{ "schema_version": "chamgap-public-criteria-1.0", "title": "High-volume energy drinks · Gap in direct evidence for increased clinical arrhythmia", "language": "en", "translation_date": "2026-10-12", "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": "Clinical harms · Materials", "question": "What is the original direction of the selected existing question?", "needed": "Exact subclaim wording, Korean/English text and question/record relationship", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Exact subclaim wording, Korean/English text and question/record relationship.", "application_exception": "Do not count trials, participants or clinical events twice because two existing checklists were prepared.", "criterion": "Connect Exact subclaim wording, Korean/English text and question/record relationship to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are our own design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "If the question changes, retain the original existing wording, previous complete version and change event separately." }, { "item_id": "N02", "question_type": "Clinical harms · Materials", "question": "How do the subclaim verdict and parent score/axes differ?", "needed": "Actual subclaim grade/note, absent score/status/axes and parent D30", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Actual subclaim grade/note, absent score/status/axes and parent D30.", "application_exception": "Do not inherit parent D30 or historical cross-checks as a subclaim score, current content-review pass or new independence certification.", "criterion": "Connect Actual subclaim grade/note, absent score/status/axes and parent D30 to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "When evidence is updated, distinguish original value preservation from actual judgment events." }, { "item_id": "N03", "question_type": "Clinical harms · Materials", "question": "What are the actual trial population and applicability boundaries?", "needed": "Healthy adults aged 18–40, baseline exclusions and selected population", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Healthy adults aged 18–40, baseline exclusions and selected population.", "application_exception": "Do not extend the healthy young population to adolescents, patients, regular medication users or all consumers.", "criterion": "Connect Healthy adults aged 18–40, baseline exclusions and selected population to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.1; detailed population conditions are Chamgap's own design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Distinguish other population materials by baseline risk, medication, age and actual eligibility." }, { "item_id": "N04", "question_type": "Clinical harms · Materials", "question": "What are the actual identity and duration of the research exposure?", "needed": "946 mL, about 300–320 mg caffeine and one exposure within one hour", "role": "Required", "role_reason": "Preparation condition retaining the original scope of 946 mL, about 300–320 mg caffeine and one exposure within one hour.", "application_exception": "Do not calculate or create can counts, caffeine equivalents, safe limits or intake/manufacturing/dosing guidance.", "criterion": "Connect 946 mL, about 300–320 mg caffeine and one exposure within one hour to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.2–3.2.3; reverse labeling and test adaptations are Chamgap's own design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Connect nominal/actual and product-specific exposure differences with the relevant outcome." }, { "item_id": "N05", "question_type": "Clinical harms · Materials", "question": "What are the identity and composition differences of drinks A/B and placebo?", "needed": "Commercial products A/B, preparation in identical containers and placebo composition", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Commercial products A/B, preparation in identical containers and placebo composition.", "application_exception": "Do not use the 2017 caffeine-comparison title to verify that the 2019 placebo was caffeine-matched.", "criterion": "Connect Commercial products A/B, preparation in identical containers and placebo composition to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "If actual product materials are provided, distinguish caffeine, combined ingredients and placebo differences." }, { "item_id": "N06", "question_type": "Clinical harms · Materials", "question": "How do 240-minute measurements differ from long-term observation?", "needed": "Measurements through 240 minutes, 30-minute intervals and acute time points", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Measurements through 240 minutes, 30-minute intervals and acute time points.", "application_exception": "Do not convert four hours into sufficient clinical-event testing duration or long-term safety.", "criterion": "Connect Measurements through 240 minutes, 30-minute intervals and acute time points to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Distinguish actual observation durations of acute biomarkers and long-term clinical outcomes in follow-up materials." }, { "item_id": "N07", "question_type": "Clinical harms · Materials", "question": "What are the sequence and analysis units of the crossover trial?", "needed": "A/B/placebo in the same 34 people, sequence allocation and carryover/period effects", "role": "Required", "role_reason": "Preparation condition retaining the original scope of A/B/placebo in the same 34 people, sequence allocation and carryover/period effects.", "application_exception": "Do not sum A/B/placebo, repeated time points or two checklists as independent participants/trials.", "criterion": "Connect A/B/placebo in the same 34 people, sequence allocation and carryover/period effects to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "When materials are supplemented, distinguish conditions/time points within the same person and crossover assumptions." }, { "item_id": "N08", "question_type": "Clinical harms · Materials", "question": "What are the common conditions and other exposures?", "needed": "Pre-visit caffeine/activity, meals, medication and measurement environment", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Pre-visit caffeine/activity, meals, medication and measurement environment.", "application_exception": "Do not invent fasting/rest/restriction times or experimental/daily-life procedures absent from the stored review summary.", "criterion": "Connect Pre-visit caffeine/activity, meals, medication and measurement environment to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; Chamgap adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Record actual common product-comparison conditions and other exposures together in follow-up materials." }, { "item_id": "N09", "question_type": "Clinical harms · Materials", "question": "How were double masking, measurement and interpretation implemented?", "needed": "Roles masked, identical containers and ECG/blood-pressure collection", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Roles masked, identical containers and ECG/blood-pressure collection.", "application_exception": "Do not newly verify masking of all interpretations or absence of measurement errors solely from identical containers or a design label.", "criterion": "Connect Roles masked, identical containers and ECG/blood-pressure collection to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Connect actual masking by role and measurement processes to outcomes." }, { "item_id": "N10", "question_type": "Clinical harms · Materials", "question": "What are the registration identifier and current registration-content status?", "needed": "2019 NCT03196908 and registration history/plans", "role": "Required", "role_reason": "Preparation condition retaining the original scope of 2019 NCT03196908 and registration history/plans.", "application_exception": "Do not copy the 2019 NCT as the 2017 registration identifier or upgrade identifier presence to registration verification/link checks.", "criterion": "Connect 2019 NCT03196908 and registration history/plans to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result links are a Chamgap application; M08 Table 8.2.a and M04 §4.6.3; Chamgap application", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "If registration materials are provided, distinguish the report, plans and actual reading scope." }, { "item_id": "N11", "question_type": "Clinical harms · Materials", "question": "What are the bibliographies and source locations of the two reports?", "needed": "Shah 2019, Fletcher 2017, PMIDs and evidence/citations", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Shah 2019, Fletcher 2017, PMIDs and evidence/citations.", "application_exception": "Do not create an evidence group absent from the stored summary for R02 or infer DOI/PMCID from article numbers.", "criterion": "Connect Shah 2019, Fletcher 2017, PMIDs and evidence/citations to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §§4.6.1–4.6.2 distinction between studies and reports; cohort/outcome links are Chamgap adaptations", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "When bibliography is supplemented, distinguish report identity, original results and change events." }, { "item_id": "N12", "question_type": "Clinical harms · Materials", "question": "What is the scope of investigator overlap and Mayo blood-pressure replication?", "needed": "Identical/unknown cohorts, author overlap and independent QTc/BP distinction", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Identical/unknown cohorts, author overlap and independent QTc/BP distinction.", "application_exception": "Do not equate investigator overlap with an identical cohort or create R03/independent clinical-arrhythmia evidence from unspecified Mayo mentions.", "criterion": "Connect Identical/unknown cohorts, author overlap and independent QTc/BP distinction to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Distinguish identical cohorts, investigator overlap, independent institutions and QTc/blood-pressure endpoint replication in new materials." }, { "item_id": "N13", "question_type": "Clinical harms · Materials", "question": "What is the original scope of support and disclosed relationships?", "needed": "2019 university support, unreported company funding and litigation expert-witness history", "role": "Required", "role_reason": "Preparation condition retaining the original scope of 2019 university support, unreported company funding and litigation expert-witness history.", "application_exception": "Do not upgrade university support or unreported company funding to new independence certification, absence of conflicts or identical 2017 support.", "criterion": "Connect 2019 university support, unreported company funding and litigation expert-witness history to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "If disclosures are provided, distinguish reports, support types, external relationships and historical/current scope." }, { "item_id": "N14", "question_type": "Clinical harms · Materials", "question": "How are original dates, Korean/English text, corrections, axes and history retained?", "needed": "2026-08-26, empty corrections/deliberation and parent/sibling context", "role": "Required", "role_reason": "Preparation condition retaining the original scope of 2026-08-26, empty corrections/deliberation and parent/sibling context.", "application_exception": "Do not fill original grades, absences, empty values or historical cross-checks with new values/current completed review.", "criterion": "Connect 2026-08-26, empty corrections/deliberation and parent/sibling context to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §§4.5 and 4.6.3; limits of the current material conversion follow the review scope and Chamgap design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "If changed materials arise, distinguish the complete pre-change original, events, versions and separate application." }, { "item_id": "N15", "question_type": "Clinical harms · Materials", "question": "Which materials were actually read?", "needed": "Complete local JSON summary, report-specific material items and unread external originals", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Complete local JSON summary, report-specific material items and unread external originals.", "application_exception": "Do not convert original citation links, historical paper descriptions or copies into external full-text reading/successful access.", "criterion": "Connect Complete local JSON summary, report-specific material items and unread external originals to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Distinguish public availability, access, acquisition, actual reading scope and dates for new materials." }, { "item_id": "N16", "question_type": "Clinical harms · Materials", "question": "Are two checklists/material items distinguished from trials/participants?", "needed": "s0/s1, two reports, conditions/time points and null unique trial/participant totals", "role": "Required", "role_reason": "Preparation condition retaining the original scope of s0/s1, two reports, conditions/time points and null unique trial/participant totals.", "application_exception": "Do not add two checklists/reports/crossover conditions or 34-person values to create an independent total sample.", "criterion": "Connect s0/s1, two reports, conditions/time points and null unique trial/participant totals to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result links are a Chamgap application; M08 Table 8.2.a, M15 §15.3 and M19 §19.1.2–19.2.4; design-specific adaptation is Chamgap’s own design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Connect additional reports by distinguishing identical/different populations, institutions and endpoints." }, { "item_id": "N17", "question_type": "Clinical harms · Materials", "question": "What is connected when new materials become available?", "needed": "Conditions, originals, observations, corrections, reading and change events", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Conditions, originals, observations, corrections, reading and change events.", "application_exception": "Original candidate pending/eligibility indications are historical; do not reactivate them as active review/waiting.", "criterion": "Connect Conditions, originals, observations, corrections, reading and change events to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §§4.5 and 4.6.3; limits of the current material conversion follow the review scope and Chamgap design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Separate actual additions/changes into complete prior originals, events, condition versions/freezing, separate application and current handoff." }, { "item_id": "N18", "question_type": "Clinical harms · Materials", "question": "What is the direct definition of clinical arrhythmia?", "needed": "Actual clinical-arrhythmia types, diagnosis/verification and symptoms/assessment", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Actual clinical-arrhythmia types, diagnosis/verification and symptoms/assessment.", "application_exception": "Do not convert QTc prolongation, blood-pressure signals or assumed palpitations into actual arrhythmia diagnoses.", "criterion": "Connect Actual clinical-arrhythmia types, diagnosis/verification and symptoms/assessment to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP; M19 §19.1.2–19.2.4; Detailed distinctions are designed by CHAMGAP", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to specify event types, verification levels, occurrence times and original populations in clinical-event materials." }, { "item_id": "N19", "question_type": "Clinical harms · Materials", "question": "Does the QTc biomarker answer increased event occurrence?", "needed": "Separation of delayed-repolarization biomarkers and direct clinical events", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Separation of delayed-repolarization biomarkers and direct clinical events.", "application_exception": "Do not convert biomarker P values/means/the 10-ms assumption into clinical-arrhythmia effects or event counts.", "criterion": "Connect Separation of delayed-repolarization biomarkers and direct clinical events to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish biomarkers, symptoms and verified events in actual clinical materials." }, { "item_id": "N20", "question_type": "Clinical harms · Materials", "question": "Are arrhythmia event counts and at-risk population denominators available?", "needed": "Clinical-event numerators, exposure/comparator denominators, baseline disease and recurrent events", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Clinical-event numerators, exposure/comparator denominators, baseline disease and recurrent events.", "application_exception": "Do not convert untested outcomes into zero events or copy 34 as a verified arrhythmia denominator.", "criterion": "Connect Clinical-event numerators, exposure/comparator denominators, baseline disease and recurrent events to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; Design-specific adaptations are designed by CHAMGAP; M19 §19.1.2–19.2.4; CHAMGAP adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish person counts, recurrent events, exposure conditions and risk periods in clinical materials." }, { "item_id": "N21", "question_type": "Clinical harms · Materials", "question": "How do four-hour measurements differ from clinical-risk periods?", "needed": "240 minutes of acute biomarker measurements, actual event follow-up and long-term exposure", "role": "Required", "role_reason": "Preparation condition retaining the original scope of 240 minutes of acute biomarker measurements, actual event follow-up and long-term exposure.", "application_exception": "Do not convert four-hour test markers into completed clinical-event testing or absence of long-term events.", "criterion": "Connect 240 minutes of acute biomarker measurements, actual event follow-up and long-term exposure to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "Design-specific harm questions in M19 §19.2; Detailed temporal relationships are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish measurement times from actual event observation/verification periods." }, { "item_id": "N22", "question_type": "Clinical harms · Materials", "question": "What are the actual contrasts and adjustments for clinical events?", "needed": "Verified energy-drink-versus-comparator arrhythmia effects and models", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Verified energy-drink-versus-comparator arrhythmia effects and models.", "application_exception": "Do not transfer biomarker A/B pairwise P values or caffeine content to between-condition clinical-event effects.", "criterion": "Connect Verified energy-drink-versus-comparator arrhythmia effects and models to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §19.2.2–19.2.4, M03 §3.2.3; CHAMGAP adaptation; M08 §8.2.2, M15 §15.3.1; CHAMGAP adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to connect actual exposure, comparator populations, baseline risk and models with events in clinical materials." }, { "item_id": "N23", "question_type": "Clinical harms · Materials", "question": "Are arrhythmia effects, CIs and power provided?", "needed": "Direct clinical-event effects, intervals, denominators and power", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Direct clinical-event effects, intervals, denominators and power.", "application_exception": "Do not calculate arrhythmia effects/CIs/risk rates from the QTc 10-ms assumption, ±, P values or n.", "criterion": "Connect Direct clinical-event effects, intervals, denominators and power to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "If direct clinical estimates are provided, connect measures, denominators, durations and uncertainty." }, { "item_id": "N24", "question_type": "Clinical harms · Materials", "question": "What are the prespecified and actual clinical-arrhythmia collection plans?", "needed": "Event plans, diagnosis, surveillance and primary/supportive/exploratory hierarchy", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Event plans, diagnosis, surveillance and primary/supportive/exploratory hierarchy.", "application_exception": "Do not inherit primary QTc or an NCT identifier as prespecified/actually tested clinical arrhythmia.", "criterion": "Connect Event plans, diagnosis, surveillance and primary/supportive/exploratory hierarchy to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M08 Table 8.2.a, M04 §4.6.3; Chamgap's own application", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish prespecified plans from actual collection and the scope of events tested in new materials." }, { "item_id": "N25", "question_type": "Clinical harms · Materials", "question": "How do event missingness, non-collection and non-reporting differ?", "needed": "Actual clinical-event collection, observation loss and reporting level", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Actual clinical-event collection, observation loss and reporting level.", "application_exception": "Do not convert currently unread/untested materials into failed access, zero arrhythmias or confirmed increased arrhythmia.", "criterion": "Connect Actual clinical-event collection, observation loss and reporting level to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish actual non-occurrence of events from absent collection/follow-up in clinical materials." }, { "item_id": "N26", "question_type": "Clinical harms · Materials", "question": "Are hospitalization, death and symptoms separate outcomes?", "needed": "Distinction among arrhythmia, palpitations/symptoms, hospitalization and death", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Distinction among arrhythmia, palpitations/symptoms, hospitalization and death.", "application_exception": "Do not assume symptoms to create new events or sum event types into a composite occurrence rate.", "criterion": "Connect Distinction among arrhythmia, palpitations/symptoms, hospitalization and death to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; Question-specific outcome adaptations are designed by CHAMGAP; CHAMGAP’s interpretation boundary, informed by M19 principles; no official causality tool was run", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to record symptoms, diagnoses, healthcare use and death as separate event outcomes." }, { "item_id": "N27", "question_type": "Clinical harms · Materials", "question": "What are applicability gaps for patients, adolescents and long-term exposure?", "needed": "Healthy young people, one high-volume exposure and other risks/durations", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Healthy young people, one high-volume exposure and other risks/durations.", "application_exception": "Do not newly establish/create clinical harms/safety, prevention/treatment or intake-care guidance for populations outside the trial.", "criterion": "Connect Healthy young people, one high-volume exposure and other risks/durations to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M03 §3.2.1–3.2.4; dose, duration and effect-modification details are Chamgap’s own design; M03 §3.2.1; detailed population conditions are Chamgap’s own design", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish actual risk populations, exposures, durations, concurrent medication and events in clinical materials." }, { "item_id": "N28", "question_type": "Clinical harms · Materials", "question": "Are earlier QTc and independent blood-pressure descriptions direct arrhythmia replication?", "needed": "Separation of 2017 biomarkers, Mayo blood pressure and direct clinical-event materials", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Separation of 2017 biomarkers, Mayo blood pressure and direct clinical-event materials.", "application_exception": "Do not transfer earlier overlapping-investigator or independent blood-pressure descriptions into independently established increased clinical arrhythmia.", "criterion": "Connect Separation of 2017 biomarkers, Mayo blood pressure and direct clinical-event materials to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M04 §4.6.1–4.6.2, M15 §15.3.1; CHAMGAP adaptation; Distinction between studies and reports in M04 §4.6.1–4.6.2; Cohort/outcome connections are CHAMGAP adaptations", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish biomarker replication, institutional independence and direct clinical-event replication in additional materials." }, { "item_id": "N29", "question_type": "Clinical harms · Materials", "question": "What is the scope of the original ? grade and untested-outcome note?", "needed": "Selected clinical-event question, original ? and gap in direct evidence", "role": "Required", "role_reason": "Preparation condition retaining the original scope of Selected clinical-event question, original ? and gap in direct evidence.", "application_exception": "Do not copy parent D in place of the selected ? or display the question “Increased clinical arrhythmia” as a confirmed observed conclusion.", "criterion": "Connect Selected clinical-event question, original ? and gap in direct evidence to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "If new direct materials are provided, preserve original ? and originals/change events while distinguishing separate judgment and preparation." }, { "item_id": "H01", "question_type": "Clinical harms · Materials", "question": "Are biomarkers, harms and clinical-event collection distinguished?", "needed": "QTc/BP testing, verified clinical events and adverse-event definitions", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of QTc/BP testing, verified clinical events and adverse-event definitions.", "application_exception": "Do not convert biomarker worsening into clinical-event counts or untested outcomes into zero adverse events.", "criterion": "Connect QTc/BP testing, verified clinical events and adverse-event definitions to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §19.1.2–19.2.4; Detailed distinctions are designed by CHAMGAP", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish measured biomarkers, symptoms and verified events in follow-up materials." }, { "item_id": "H02", "question_type": "Clinical harms · Materials", "question": "What are harm timing and actual exposure?", "needed": "Single research exposure, acute measurement and event-risk periods", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Single research exposure, acute measurement and event-risk periods.", "application_exception": "Do not convert the original exposure into recommended intake, a safe dose or prevention/treatment methods.", "criterion": "Connect Single research exposure, acute measurement and event-risk periods to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §19.2 design-specific harm questions; timing details are Chamgap-designed", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish exposure, testing times and clinical-event risk periods in harm materials." }, { "item_id": "H03", "question_type": "Clinical harms · Materials", "question": "How do between-condition biomarker differences differ from clinical harm comparisons?", "needed": "Biomarker outcomes for A/B/placebo and clinical-event comparisons", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Biomarker outcomes for A/B/placebo and clinical-event comparisons.", "application_exception": "Do not transfer biomarker P values to clinical-harm P values or between-condition event risks.", "criterion": "Connect Biomarker outcomes for A/B/placebo and clinical-event comparisons to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §§19.2.2–19.2.4 and M03 §3.2.3; Chamgap adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to connect direct harm materials using event definitions, comparisons and intervals separate from biomarkers." }, { "item_id": "H04", "question_type": "Clinical harms · Materials", "question": "What are safety and event denominators?", "needed": "34 people and actual denominators by condition/time/event", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of 34 people and actual denominators by condition/time/event.", "application_exception": "Do not multiply crossover conditions/time measurements into participant counts or calculate risk rates from unread materials.", "criterion": "Connect 34 people and actual denominators by condition/time/event to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish person, condition, time-point and measurement/event denominators in originals." }, { "item_id": "H05", "question_type": "Clinical harms · Materials", "question": "What are alternative harm factors and ingredient-specific attribution?", "needed": "Caffeine, combined ingredients, baseline/concurrent exposures and relatedness", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Caffeine, combined ingredients, baseline/concurrent exposures and relatedness.", "application_exception": "Do not attribute every signal to caffeine alone or established harm from a particular ingredient, or invent mechanisms/event cases.", "criterion": "Connect Caffeine, combined ingredients, baseline/concurrent exposures and relatedness to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §§19.2.2–19.2.4 design considerations; detailed confounding records are Chamgap-designed", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish whole products, ingredient-specific attribution and alternative factors in direct harm materials." }, { "item_id": "H06", "question_type": "Clinical harms · Materials", "question": "Are unread, untested, unreported and zero events distinguished?", "needed": "Actual reading level, untested clinical endpoints and original reports", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Actual reading level, untested clinical endpoints and original reports.", "application_exception": "Do not convert currently unread materials into zero side effects, failed access, an absent paper or confirmed direct clinical harm.", "criterion": "Connect Actual reading level, untested clinical endpoints and original reports to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §§19.1.2–19.2.4 and M04 §4.6.3; Chamgap adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Only for provided materials, connect actual zero events, missingness, non-reporting and non-collection with locations/durations." }, { "item_id": "H07", "question_type": "Clinical harms · Materials", "question": "Are harms across reports, conditions and two checklists protected from duplicate counting?", "needed": "2017/2019, author overlap, conditions/time points and two questions in the same summary", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of 2017/2019, author overlap, conditions/time points and two questions in the same summary.", "application_exception": "Do not equate investigator overlap with the same cohort or count two bibliographies/checklists as new independent-event replication.", "criterion": "Connect 2017/2019, author overlap, conditions/time points and two questions in the same summary to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "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’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish repeated reports of the same event from different populations/new events in harm materials." }, { "item_id": "H08", "question_type": "Clinical harms · Materials", "question": "What are safety gaps for long-term use and vulnerable populations?", "needed": "Selected healthy adults, single high-volume exposure and chronic use/patients/adolescents", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Selected healthy adults, single high-volume exposure and chronic use/patients/adolescents.", "application_exception": "Do not create safe-dose, intake/care, arrhythmia prevention/treatment or medical-replacement procedures.", "criterion": "Connect Selected healthy adults, single high-volume exposure and chronic use/patients/adolescents to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "M19 §§19.1.2–19.2.4; Chamgap adaptation", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to record direct materials together with actual exposure, population and observation duration." }, { "item_id": "H09", "question_type": "Clinical harms · Materials", "question": "Are signals distinguished from direct causal or clinical confirmation?", "needed": "Biomarker signals, original D, direct clinical ? and unverified information", "role": "Supporting harm information", "role_reason": "Preparation condition retaining the original scope of Biomarker signals, original D, direct clinical ? and unverified information.", "application_exception": "Do not label original question wording as proven observation or combine biomarkers and clinical events into a new harm assessment.", "criterion": "Connect Biomarker signals, original D, direct clinical ? and unverified information to actual endpoints, exposures, comparisons, time, denominators and reading levels; distinguish unverified information.", "basis": "Chamgap interpretive boundary informed by M19 principles; no formal causality tool was run", "condition_origin": "Chamgap’s own design and production from original material; content review is separately assigned", "proposed_research": "Retain a proposal to distinguish observation, relatedness, direct clinical-effect levels and change events in additional materials." } ] }