{ "title": "Single-active oral pantothenic acid (vitamin B5) exposure × risk of new or worsened diarrhea adverse events", "criteria_version": "NGM-v3102-SOLE-ORAL-B5-DIARRHEA-SAFETY-1.1", "criteria_date": "2026-10-05", "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 of the intervention.", "review_level": "Historical reuse of the 1585 method HTML copies (5), their actual original bytes/SHA and the principles recorded at the time; no new reading of method full texts or execution of a formal assessment/clinical certification" }, { "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 and link studies and reports; do not omit a study solely because outcomes are unreported.", "review_level": "Historical reuse of the 1585 method HTML copies (5), their actual original bytes/SHA and the principles recorded at the time; no new reading of method full texts or execution of a formal assessment/clinical certification" }, { "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": "Fix the outcome and effect of interest when reviewing randomization, deviations, missingness, measurement and selective reporting.", "review_level": "Historical reuse of the 1585 method HTML copies (5), their actual original bytes/SHA and the principles recorded at the time; no new reading of method full texts or execution of a formal assessment/clinical certification" }, { "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 application. Sample size alone does not determine precision.", "review_level": "Historical reuse of the 1585 method HTML copies (5), their actual original bytes/SHA and the principles recorded at the time; no new reading of method full texts or execution of a formal assessment/clinical certification" }, { "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 designs, populations and follow-up that differ from those for efficacy. Case reports do not establish incidence.", "review_level": "Historical reuse of the 1585 method HTML copies (5), their actual original bytes/SHA and the principles recorded at the time; no new reading of method full texts or execution of a formal assessment/clinical certification" } ], "status_dictionary": { "Met": "The specific narrow condition concerning identity/attribution, original values and scope/reading records is met. This does not establish efficacy, definitive causality, absence of risk or current external full-text verification.", "Partly verified": "Related observations are preserved, but some aspects of actual exposure/definitions, denominators, methods or comparison with original materials are unverified.", "Unverified": "This could not be established within the current archived materials and the scope verified at the time. It does not mean 0 risk, worldwide absence of evidence or access failure.", "Not reported": "Limited to non-reporting in manuscripts actually read/the stated scope of historical verification. It does not extend to the entirety of unread external full texts.", "Conflicting information": "Identifies inconsistent preserved descriptions of the same fact. Different exposure conditions or different roles of documents are not themselves conflicts.", "Inaccessible": "Used only for actual access failure in this review. As external access was not attempted in this review, historical failures are not converted into this state.", "Review incomplete": "Limited to the absence of current external comparison; it does not describe the entirety of the local archived-summary/model review that was actually completed.", "Not applicable": "Limited to the exclusion role for the specified exposure/endpoint. It is not a substitute for unverified/unread, no risk or no human data." }, "schema_version": "chamgap-public-criteria-1.0", "condition_origin": "Chamgap’s own application conditions", "requirements": [ { "item_id": "N01", "question_type": "Diarrhea harm · Is this table's safety-only, efficacy-not-applicable contract preserved?", "question": "Is this table's safety-only, efficacy-not-applicable contract preserved?", "needed": "Original safety-only display and assessment contract", "role": "Required", "role_reason": "This is needed to avoid converting a harm signal into a numerical efficacy/risk grade.", "application_exception": "The original grade ? and empty score value, and document quality B, are historical values. The absent 7-axis/no_human fields are not created.", "criterion": "Link safety_only, efficacy not_applicable, and framework false to their original locations without assigning a new score or efficacy display.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C09: M04 §4.5, §4.6.3; limitations of the current material conversion reflect the user-defined scope and self-designed rules / H09: Chamgap's own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to the harm question: This is needed to avoid converting a harm signal into a numerical efficacy/risk grade. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare the display fields with the boundaries on applying historical values." }, { "item_id": "N02", "question_type": "Diarrhea harm · What are the separate question and its inclusion/exclusion scope?", "question": "What are the separate question and its inclusion/exclusion scope?", "needed": "Scope of the original claim/population/exposure/endpoint", "role": "Required", "role_reason": "Fix the selected question about diarrhea from an oral single-active-ingredient product rather than the safety of the ingredient as a whole.", "application_exception": "Separate dose, meal, and duration conditions within the same question without extending it to all other harms/efficacy.", "criterion": "Link the original claim to adults, B5 as the sole active ingredient, oral exposure, and new/worsened diarrhea.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / H09: Chamgap's own interpretive boundaries. M19 principles are referenced; no formal causality tool was applied. Reason for application to the harm question: Fix the selected question about diarrhea from an oral single-active-ingredient product rather than the safety of the ingredient as a whole. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare the boundaries of the separate question with adjacent questions." }, { "item_id": "N03", "question_type": "Diarrhea harm · Was the directly studied preparation distinguished from other B5-related substances?", "question": "Was the directly studied preparation distinguished from other B5-related substances?", "needed": "Identity of the substance/product composition/source ingredients/additives", "role": "Required", "role_reason": "This is needed to avoid attributing events involving other molecules or combination products to B5 alone.", "application_exception": "Pantethine, pantetheine, dexpanthenol/panthenol, B-complex products, and multivitamins are not combined as the same exposure.", "criterion": "Explain inclusion/exclusion of the directly studied preparation and other substances/compositions.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed confounding records are self-designed. Reason for application to the harm question: This is needed to avoid attributing events involving other molecules or combination products to B5 alone. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review whether the composition and molecule match for each product." }, { "item_id": "N04", "question_type": "Diarrhea harm · Is the acid/salt mass basis of the stated administered dose clear?", "question": "Is the acid/salt mass basis of the stated administered dose clear?", "needed": "Original tablet label, dosing table, and evidence for the acid/salt mass basis", "role": "Required", "role_reason": "This is needed to avoid converting the nominal dose into an actual acid/salt amount or toxicity threshold.", "application_exception": "Do not newly calculate the actual clinical dose from the explanation of 550 mg of calcium salt versus 500 mg of free base in the original text.", "criterion": "Separate the label, dosing table, and pharmacokinetic explanation, leaving the unclear mass basis unresolved.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / H04: M19 §19.1.2–19.2.4; self-adapted application. Reason for application to the harm question: This is needed to avoid converting the nominal dose into an actual acid/salt amount or toxicity threshold. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare how the same preparation's dose is stated across documents." }, { "item_id": "N05", "question_type": "Diarrhea harm · How are the nominal doses in the single-dose conditions distinguished?", "question": "How are the nominal doses in the single-dose conditions distinguished?", "needed": "Nominal dose and dosing/meal records by condition", "role": "Required", "role_reason": "This is needed to avoid combining different dose conditions into a single exposure or a minimum harmful dose.", "application_exception": "Do not interpret nominal doses as risk thresholds or recommended doses for individuals.", "criterion": "Link the single doses and fasted/fed conditions exactly as reported in the paper.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are self-designed. Reason for application to the harm question: This is needed to avoid combining different dose conditions into a single exposure or a minimum harmful dose. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the link between exposure under each condition and the AE table." }, { "item_id": "N06", "question_type": "Diarrhea harm · Are repeated exposure and follow-up periods separated from single dosing?", "question": "Are repeated exposure and follow-up periods separated from single dosing?", "needed": "Repeated dosing, adherence, and AE follow-up schedule", "role": "Required", "role_reason": "This is needed to avoid extending a short repeated-dose condition to long-term safety.", "application_exception": "Do not convert the 14-day repeated exposure and follow-up through day 22 into the same period.", "criterion": "Distinguish repeated dosing at 2,000 mg/day for 14 days from follow-up through day 9 for single dosing/day 22 for repeated dosing.", "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are self-designed. Reason for application to the harm question: This is needed to avoid extending a short repeated-dose condition to long-term safety. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review exposure duration and observation duration as separate dimensions." }, { "item_id": "N07", "question_type": "Diarrhea harm · Are the directly studied population and baseline diarrhea status verified?", "question": "Are the directly studied population and baseline diarrhea status verified?", "needed": "Table of inclusion/exclusion, sex, baseline diarrhea/diseases, and medications", "role": "Required", "role_reason": "This is needed to avoid applying data from healthy people directly to all adults or to worsening of baseline diarrhea.", "application_exception": "Do not convert the description of participants as healthy into proof of absence of diarrhea in individuals or safety in special populations.", "criterion": "Distinguish the healthy population aged 18–55 from individual baseline GI/selection information.", "basis": "C04: M03 §3.2.1; detailed population conditions are self-designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed confounding records are self-designed / H08: M19 §19.1.2–19.2.4; self-adapted application. Reason for application to the harm question: This is needed to avoid applying data from healthy people directly to all adults or to worsening of baseline diarrhea. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review limitations on applicability according to the population and baseline symptoms." }, { "item_id": "N08", "question_type": "Diarrhea harm · Can the 40 participants be distinguished from the single-dose and repeated-dose completion denominators?", "question": "Can the 40 participants be distinguished from the single-dose and repeated-dose completion denominators?", "needed": "Recruitment/allocation/exposure/completion/analysis flow and participant linkage by condition", "role": "Required", "role_reason": "This is needed to avoid reusing the overall study size as the diarrhea analysis denominator for every condition.", "application_exception": "Fed redosing involved the same 8 participants, and the single-dose/repeated-dose conditions are not counted as independent studies.", "criterion": "Separately link completion by 40 participants overall, 32 in the single-dose part, and 8 in the repeated-dose part, and the report of 8 participants per condition.", "basis": "C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is self-adapted / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is self-designed / H04: M19 §19.1.2–19.2.4; self-adapted application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; self-adapted application. Reason for application to the harm question: This is needed to avoid reusing the overall study size as the diarrhea analysis denominator for every condition. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare participant flow with the analysis denominator for each condition." }, { "item_id": "N09", "question_type": "Diarrhea harm · Are the participants, sequence, and actual washout period for fed redosing consistently verified?", "question": "Are the participants, sequence, and actual washout period for fed redosing consistently verified?", "needed": "Original abstract, methods, and individual dosing sequence/washout schedule", "role": "Required", "role_reason": "This is needed to avoid interpreting conditions in the same people with changes in meal status and sequence as randomized control groups.", "application_exception": "Do not correct 2 weeks in the abstract and 2–3 weeks in the methods to a single confirmed washout value or compare them as independent groups.", "criterion": "Verify the dosing sequence and actual washout schedule for the same 8 participants, and compare whether the duration descriptions in the abstract/methods are consistent. If differences in the duration descriptions or an unverified actual schedule remain, do not treat the duration as consistently verified.", "basis": "C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is self-adapted / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation of checks are self-designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are self-designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; self-adapted application. Reason for application to the harm question: This is needed to avoid interpreting conditions in the same people with changes in meal status and sequence as randomized control groups. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review differences in sequence/washout/meal status and inconsistencies in descriptions within the same family." }, { "item_id": "N10", "question_type": "Diarrhea harm · What are the definition and coding criteria for diarrhea?", "question": "What are the definition and coding criteria for diarrhea?", "needed": "Diarrhea AE definition, coding/diagnostic criteria, and records of stool frequency/form", "role": "Required", "role_reason": "This is needed to avoid recoding general GI discomfort or loose stools as confirmed diarrhea.", "application_exception": "Do not equate a MedDRA term with diagnostic criteria based on stool frequency/form or with a clinical diagnosis.", "criterion": "Distinguish the MedDRA 21.0 diarrhea category from the separate gap in diagnostic criteria.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed / H01: M19 §19.1.2–19.2.4; detailed ascertainment is self-designed. Reason for application to the harm question: This is needed to avoid recoding general GI discomfort or loose stools as confirmed diarrhea. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Propose a review that re-extracts the original table using the same event definition." }, { "item_id": "N11", "question_type": "Diarrhea harm · Are data available to distinguish new diarrhea from worsening of existing diarrhea?", "question": "Are data available to distinguish new diarrhea from worsening of existing diarrhea?", "needed": "Baseline diarrhea and change criteria, and an AE table separating new/worsened cases", "role": "Required", "role_reason": "This is needed to examine whether the original event data actually distinguish the two scopes of the original question: occurrence and worsening.", "application_exception": "Do not reclassify events that are currently unseparated as all new or all worsened.", "criterion": "Link baseline symptoms with person counts and ascertainment data for new/worsened cases.", "basis": "C04: M03 §3.2.1; detailed population conditions are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed / H01: M19 §19.1.2–19.2.4; detailed ascertainment is self-designed. Reason for application to the harm question: This is needed to examine whether the original event data actually distinguish the two scopes of the original question: occurrence and worsening. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review separated records based on the same ascertainment criteria." }, { "item_id": "N12", "question_type": "Diarrhea harm · Can diarrhea collection methods, severity, and differences in detection be verified?", "question": "Can diarrhea collection methods, severity, and differences in detection be verified?", "needed": "AE collection form/questioning frequency, blinding/ascertainment, and severity table", "role": "Required", "role_reason": "This is needed to avoid assuming that categorized reported values represent systematically and completely collected events.", "application_exception": "An open-label trial/use of MedDRA alone does not establish spontaneous versus systematic collection or blinded ascertainment.", "criterion": "Verify diarrhea-specific collection tools, frequency, severity, and ascertainment methods.", "basis": "H01: M19 §19.1.2–19.2.4; detailed ascertainment is self-designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; self-adapted application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed. Reason for application to the harm question: This is needed to avoid assuming that categorized reported values represent systematically and completely collected events. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review collection methods and differences in detection/omission." }, { "item_id": "N13", "question_type": "Diarrhea harm · Were nausea, vomiting, and abdominal discomfort kept separate from diarrhea?", "question": "Were nausea, vomiting, and abdominal discomfort kept separate from diarrhea?", "needed": "Original AE categories by endpoint and a table of people/events", "role": "Required", "role_reason": "This is needed to avoid adding other GI events to the person count or magnitude of harm for the selected endpoint.", "application_exception": "Overall AEs or composite GI symptoms do not replace diarrhea-only results.", "criterion": "Separate attribution of results for diarrhea and other GI categories.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is self-designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is self-designed / H01: M19 §19.1.2–19.2.4; detailed ascertainment is self-designed. Reason for application to the harm question: This is needed to avoid adding other GI events to the person count or magnitude of harm for the selected endpoint. No formal causality/harm grading assessment or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review multiple events in the same person and different categories separately." }, { "item_id": "N14", "question_type": "Diarrhea harm · What is the direct diarrhea report under the 5,000 mg fasted condition?", "question": "What is the direct diarrhea report under the 5,000 mg fasted condition?", "needed": "Original Table 6 and the relevant person's AE record", "role": "Required", "role_reason": "This is needed to acknowledge the direct signal while distinguishing reported observations from causal risk.", "application_exception": "Do not convert 1/8 into a general incidence rate, risk ratio, individual probability, or minimum harmful dose.", "criterion": "Attribute the report in Table 6 for the paper-labeled 5,000 mg fasted single-dose condition (1/8 participants) to the specified condition.", "basis": "H01: M19 §19.1.2–19.2.4; detailed distinctions were internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed. Reason for application to the harm question: needed to acknowledge the direct signal while distinguishing reported observations from causal risk. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the link between the reported people, exposure conditions, and event definition." }, { "item_id": "N15", "question_type": "Diarrhea harm · Are conditions with 0/8 reports also retained?", "question": "Are conditions with 0/8 reports also retained?", "needed": "Condition-specific Table 6 and the scope of exposure/follow-up and collection", "role": "Required", "role_reason": "Needed to avoid selecting only positive signals or converting an absence of reports into an absence of risk.", "application_exception": "For the same 8 participants, the fed-dosing 0/8 is not a preventive effect, and the 0/8 under other doses/repeated dosing is not a safety threshold.", "criterion": "Retain the 0/8 records for each lower single dose, repeated dosing, and subsequent fed dosing, together with their limitations.", "basis": "C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was internally designed / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied. Reason for application to the harm question: needed to avoid selecting only positive signals or converting an absence of reports into an absence of risk. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review reported 0 within the scope of missingness/detection and duration." }, { "item_id": "N16", "question_type": "Diarrhea harm · Can the reported numbers of people, repeated events, and exposure-time denominators be distinguished?", "question": "Can the reported numbers of people, repeated events, and exposure-time denominators be distinguished?", "needed": "Condition-specific person/event counts, follow-up/exposure time, and missing data", "role": "Required", "role_reason": "Needed to avoid confusing the different denominators for reports of people and event frequency/incidence rates.", "application_exception": "Do not replace the 8 participants per condition with the total of 40 participants or 16 participants obtained from fed + fasted dosing.", "criterion": "Distinguish the original denominator for reported people and repeated-event/time information from values that are absent.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed / H04: M19 §19.1.2–19.2.4; internal application. Reason for application to the harm question: needed to avoid confusing the different denominators for reports of people and event frequency/incidence rates. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review interpretation of harm frequency with people, events, and time kept separate." }, { "item_id": "N17", "question_type": "Diarrhea harm · Was diarrhea risk compared with an appropriate unexposed/placebo group?", "question": "Was diarrhea risk compared with an appropriate unexposed/placebo group?", "needed": "Unexposed/appropriate comparator data with matching event definitions/follow-up", "role": "Required", "role_reason": "Needed to avoid describing a report without a comparison as the magnitude of a risk increase.", "application_exception": "Retain the signal even in the absence of comparative data. Do not substitute a randomized placebo group for fixed-sequence/redosing with food.", "criterion": "Link the actual comparator structure to whether comparative risk can be estimated or remains unverified.", "basis": "H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied / C05: M03 §3.2.2–3.2.3; reverse-direction markers and test adaptations were internally designed. Reason for application to the harm question: needed to avoid describing a report without a comparison as the magnitude of a risk increase. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the population/confounding and sequence/meal differences in existing comparative observations." }, { "item_id": "N18", "question_type": "Diarrhea harm · Is the temporal link between diarrhea onset/recovery and exposure verified?", "question": "Is the temporal link between diarrhea onset/recovery and exposure verified?", "needed": "Individual logs of dosing, blood sampling/meals, and diarrhea onset/recovery", "role": "Required", "role_reason": "Distinguish reports after exposure from specific onset/recovery and causal clues from re-exposure.", "application_exception": "Do not convert the record that all AEs had resolved by the end into diarrhea-specific recovery dates or evidence of positive dechallenge/rechallenge.", "criterion": "Link diarrhea-specific onset, duration, and recovery with actual dosing times.", "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed / H02: design-specific harm questions in M19 §19.2; details of temporal relationships were internally designed / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied. Reason for application to the harm question: distinguish reports after exposure from specific onset/recovery and causal clues from re-exposure. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the temporal sequence and alternative explanations for each event." }, { "item_id": "N19", "question_type": "Diarrhea harm · Is the investigator's wording on relatedness kept separate from established causality?", "question": "Is the investigator's wording on relatedness kept separate from established causality?", "needed": "The basis for individual AE relatedness assessments and records of alternative causes", "role": "Required", "role_reason": "Needed to retain the original relatedness assessment without extending it to formal causality certification.", "application_exception": "The Caution safety label is not confirmation of an individual’s cause or a quantitative causality score.", "criterion": "Distinguish the original report's statements on relatedness from uncertainty and gaps concerning alternative causes.", "basis": "H05: design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed. Reason for application to the harm question: needed to retain the original relatedness assessment without extending it to formal causality certification. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the original wording on relatedness and the level of evidence for timing/alternative causes." }, { "item_id": "N20", "question_type": "Diarrhea harm · Were alternative explanations such as concurrent exposure, diet, and infection reviewed?", "question": "Were alternative explanations such as concurrent exposure, diet, and infection reviewed?", "needed": "Records of medications/supplements, diet, meals, excipients, and infection/baseline symptoms", "role": "Required", "role_reason": "Needed to avoid eliminating background exposures and alternative causes solely on the basis of identification as a single-active-ingredient product.", "application_exception": "Do not extend the prohibition of other medications/supplements to control of all diet, excipients, and infections.", "criterion": "Link medication/supplement restrictions and uncontrolled diet with gaps concerning alternative causes.", "basis": "H05: design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction markers and test adaptations were internally designed. Reason for application to the harm question: needed to avoid eliminating background exposures and alternative causes solely on the basis of identification as a single-active-ingredient product. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review alternative exposures and potential confounding for the same event." }, { "item_id": "N21", "question_type": "Diarrhea harm · Are discontinuation/serious AE reports distinguished from detailed participant flow?", "question": "Are discontinuation/serious AE reports distinguished from detailed participant flow?", "needed": "Diarrhea-specific reasons for discontinuation/dropout, periods without collection, and participant flow", "role": "Required", "role_reason": "Needed to avoid converting a general safety summary into an absence of diarrhea-specific missingness or long-term safety.", "application_exception": "No deaths, serious AEs, or AE discontinuations is not proof of 0 diarrhea events or complete event collection for every participant.", "criterion": "Retain the original general safety summary separately from diarrhea-specific discontinuation/missingness and flow gaps.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / H01: M19 §19.1.2–19.2.4; detailed distinctions were internally designed. Reason for application to the harm question: needed to avoid converting a general safety summary into an absence of diarrhea-specific missingness or long-term safety. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review differences in event detection between completer data and those who discontinued/had missing data." }, { "item_id": "N22", "question_type": "Diarrhea harm · Are the registration, protocol, analysis plan, and scope of prespecification verified?", "question": "Are the registration, protocol, analysis plan, and scope of prespecification verified?", "needed": "Registration, protocol, SAP, and records of diarrhea prespecification/changes", "role": "Required", "role_reason": "Needed to review the possibility of selective reporting and the scope of prespecified/post hoc analyses.", "application_exception": "Do not convert current lack of verification and historical access failures into established absence of preregistration or confirmed deviation from the plan.", "criterion": "Distinguish the scope actually verified in the registration/protocol/SAP from what remains unverified.", "basis": "C09: M04 §4.5, §4.6.3; restrictions on the current data transformation follow the user-defined scope and internal design / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for application to the harm question: needed to review the possibility of selective reporting and the scope of prespecified/post hoc analyses. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare specified endpoints, collection, and public reporting against the plan for consistency." }, { "item_id": "N23", "question_type": "Diarrhea harm · Are risk differences, risk ratios, CIs, and criteria for interpreting harm verified?", "question": "Are risk differences, risk ratios, CIs, and criteria for interpreting harm verified?", "needed": "Original comparative estimates, denominators, CIs/uncertainty, and clinical harm criteria", "role": "Required", "role_reason": "Needed to avoid converting a small descriptive report into quantitative comparative risk or a minimum harmful dose.", "application_exception": "Do not newly calculate risk differences/risk ratios, incidence rates, CIs, P, or NNH that are absent from the existing data.", "criterion": "Distinguish reported observations from gaps in formal comparative estimates/uncertainty and harm criteria.", "basis": "H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H04: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed. Reason for application to the harm question: needed to avoid converting a small descriptive report into quantitative comparative risk or a minimum harmful dose. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the scope of interpretation of estimates with the same event/comparator/duration." }, { "item_id": "N24", "question_type": "Diarrhea harm · What is the scope of the absence of recorded side effects in the arthritis trial?", "question": "What is the scope of the absence of recorded side effects in the arthritis trial?", "needed": "The original GPRG diarrhea/AE event table and dosing, population, and collection methods", "role": "Required", "role_reason": "Needed to retain contrary context without converting a 2nd-hand general side-effect statement into a diarrhea event table.", "application_exception": "The original event table not having been acquired is not a new access failure in this work, and an absence of recorded side effects is not substituted with 0 diarrhea events.", "criterion": "Separate SCF's summary of dose escalation over 8 weeks in arthritis from the access scope of the PubMed bibliographic record.", "basis": "C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions were internally designed / H07: M04 §4.6.1–4.6.2; adaptations for harm data were internally designed. Reason for application to the harm question: needed to retain contrary context without converting a 2nd-hand general side-effect statement into a diarrhea event table. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare the general AE statement in the 2nd-hand summary against the original event definition/table." }, { "item_id": "N25", "question_type": "Diarrhea harm · Are the overall and arm-specific participants and analysis denominators in the arthritis study consistently verified?", "question": "Are the overall and arm-specific participants and analysis denominators in the arthritis study consistently verified?", "needed": "Original participant flow, arm-specific allocation/analysis tables, and SCF's cited statement", "role": "Required", "role_reason": "Needed to avoid arbitrarily correcting different statements of the total or using them as established analysis denominators.", "application_exception": "47+46=93 is historical arithmetic already present in the original summary. Do not correct the total through new calculations/selection.", "criterion": "Check whether the actual definitions and counts of overall and arm-specific allocation/completion/analysis denominators are consistently verified in the original tables. If the inconsistency between 94 participants and arm-specific counts of 47/46 participants remains, do not treat them as established denominators.", "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was internally designed. Reason for application to the harm question: needed to avoid arbitrarily correcting different statements of the total or using them as established analysis denominators. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Check each denominator's definition/location and conflicting descriptions against the original tables." }, { "item_id": "N26", "question_type": "Diarrhea harm · What limitations apply to the reused NIH example of 10 g/day?", "question": "What limitations apply to the reused NIH example of 10 g/day?", "needed": "The relevant NIH section and underlying original cases and exposure/event data", "role": "Required", "role_reason": "Needed to avoid interpreting an official general safety statement as a new event rate or toxicity threshold.", "application_exception": "Do not convert the official NIH discussion into a new clinical trial or an allowable/recommended intake of 10 g/day.", "criterion": "Retain the example of very high intake at 10 g/day and the gaps concerning cases/formulation, duration, and denominators.", "basis": "C03: data collection/selection principles in M04 §4.5–4.6; separation of access and reading and the hyperlink contract were internally designed / H07: M04 §4.6.1–4.6.2; adaptations for harm data were internally designed / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied. Reason for application to the harm question: needed to avoid interpreting an official general safety statement as a new event rate or toxicity threshold. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Trace the original observation lineage, actual exposure, and endpoint evidence underlying the general discussion." }, { "item_id": "N27", "question_type": "Diarrhea harm · Are historical summaries of 10–20 g/day kept from being counted as independent human replications?", "question": "Are historical summaries of 10–20 g/day kept from being counted as independent human replications?", "needed": "SCF/CIR citation lineage, Elder 1987, and underlying original cases", "role": "Required", "role_reason": "Needed to avoid summing repeated citations by SCF/CIR/NIH as distinct established studies.", "application_exception": "The number of official/expert documents and summary family_id are not the number of independent clinical cases/trials.", "criterion": "Separate overlapping summary lineages of historical reports from the lack of verification of original cases.", "basis": "C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application / H07: M04 §4.6.1–4.6.2; adaptations for harm data were internally designed. Reason for application to the harm question: needed to avoid summing repeated citations by SCF/CIR/NIH as distinct established studies. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Check repeated citations/duplication of the same original observations and whether the participants are independent." }, { "item_id": "N28", "question_type": "Diarrhea harm · Is the meaning of insufficient data behind the absence of an established upper intake level preserved?", "question": "Is the meaning of insufficient data behind the absence of an established upper intake level preserved?", "needed": "The relevant official edition/harm assessment section and the basis for data insufficiency", "role": "Required", "role_reason": "Needed to avoid mistaking inability to derive an upper intake level for unlimited safety or a legally permitted therapeutic dose.", "application_exception": "The wording of the official assessment and the edition checked are historical in scope and do not represent a current lookup of the latest regulations in this work.", "criterion": "Link the UL-related wording and dates in FNB 1998 and EFSA version 11(2025-08).", "basis": "C09: M04 §4.5, §4.6.3; restrictions on the current data transformation follow the user-defined scope and internal design / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap’s own interpretive boundary. References M19 principles; no formal causality tool was applied. Reason for application to the harm question: needed to avoid mistaking inability to derive an upper intake level for unlimited safety or a legally permitted therapeutic dose. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the limitations on deriving a UL in each edition checked and whether it has been updated." }, { "item_id": "N29", "question_type": "Diarrhea harm · Are adequate intake and high-dose diarrhea signals kept separate?", "question": "Are adequate intake and high-dose diarrhea signals kept separate?", "needed": "Populations/definitions of nutritional reference values and data on high-dose preparations", "role": "Required", "role_reason": "Needed to avoid converting a nutritional adequacy reference into a diarrhea threshold or instructions for an individual's high-dose treatment.", "application_exception": "The values of 5 for adults, 6 for pregnancy and 7 mg/day for lactation are not risk values from the same clinical exposure group.", "criterion": "Preserve the distinction between the nutritional purpose of the AI values and high-dose single-active-ingredient exposure.", "basis": "C05: M03 §3.2.2–3.2.3; reverse indicators and test adaptations are internally designed / H08: M19 §19.1.2–19.2.4; internally applied / H09: Chamgap’s own interpretive boundary. M19 principles are referenced; no formal causality tool was applied. Reason for application to the harm question: Needed to avoid converting nutritional adequacy references into a diarrhea threshold or personal high-dose treatment instructions. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the purpose, target population and actual exposure scope of each reference separately." }, { "item_id": "N30", "question_type": "Diarrhea harm · Is the boundary on applying the CIR cosmetic assessment to oral use preserved?", "question": "Is the boundary on applying the CIR cosmetic assessment to oral use preserved?", "needed": "CIR review scope, toxicology section and underlying oral-use references", "role": "Required", "role_reason": "Needed to avoid converting a safety assessment with a different route/purpose into authorization/safety certification of a single-active oral preparation.", "application_exception": "Historical oral-use reports cited in a cosmetic review do not provide grounds for authorization of all oral preparations.", "criterion": "Distinguish CIR’s cosmetic-review scope from the role of its historical oral-use summaries.", "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / H07: M04 §4.6.1–4.6.2; adaptation to harm data is internally designed / H09: Chamgap’s own interpretive boundary. M19 principles are referenced; no formal causality tool was applied. Reason for application to the harm question: Needed to avoid converting a safety assessment with a different route/purpose into authorization/safety certification of a single-active oral preparation. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review the assessment’s jurisdiction/route, citation lineage and evidence for oral-exposure events separately." }, { "item_id": "N31", "question_type": "Diarrhea harm · Are pantethine and the acne product with unestablished composition excluded?", "question": "Are pantethine and the acne product with unestablished composition excluded?", "needed": "Identity of the product’s ingredients/formulation and historical exclusion extraction", "role": "Required", "role_reason": "Needed to avoid transferring the tolerability of a different molecule/product into direct harm evidence for this question.", "application_exception": "Not applicable is the denominator’s role within the exclusion scope; it does not mean 0 people, no risk or no human research.", "criterion": "Link the Evans record of a different molecule and the Yang record of unestablished single-active composition as separate grounds for exclusion.", "basis": "C05: M03 §3.2.2–3.2.3; reverse indicators and test adaptations are internally designed / C02: Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is internally applied / H07: M04 §4.6.1–4.6.2; adaptation to harm data is internally designed. Reason for application to the harm question: Needed to avoid transferring the tolerability of a different molecule/product into direct harm evidence for this question. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review substance identity, product composition and the transferability of diarrhea endpoints separately." }, { "item_id": "N32", "question_type": "Diarrhea harm · Is funding/conflict-of-interest attribution clear for each study/review?", "question": "Is funding/conflict-of-interest attribution clear for each study/review?", "needed": "Original Funding/COI, support/product provision and funding records for underlying cases", "role": "Required", "role_reason": "Needed to avoid hiding developer support or transferring another review’s funding to support for the original cases.", "application_exception": "Disclosed interests alone do not determine study invalidation, effect-size adjustment or a new harm grade.", "criterion": "Preserve Rao’s and the CIR review’s funding/relationships separately from the unverified information for original cases.", "basis": "C10: Chamgap’s own independence/attribution condition. The formal methods sections used in this pilot do not warrant every detail of this item / H07: M04 §4.6.1–4.6.2; adaptation to harm data is internally designed. Reason for application to the harm question: Needed to avoid hiding developer support or transferring another review’s funding to support for the original cases. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review relationships relevant to data production/reporting structures and support that remains unknown." }, { "item_id": "N33", "question_type": "Diarrhea harm · Is there direct harm evidence for long-term exposure and vulnerable populations?", "question": "Is there direct harm evidence for long-term exposure and vulnerable populations?", "needed": "Long-term follow-up and direct diarrhea/exposure/comparator data by population", "role": "Required", "role_reason": "Needed to avoid extending a short study in healthy people to long-term safety during pregnancy/lactation, in children or in older people/those with disease.", "application_exception": "Indirect documents/AI values and brief reports of 0/8 do not demonstrate absence of risk in each population.", "criterion": "Separate the scope of healthy people aged 18–55 and short exposure from gaps for other populations/long-term exposure.", "basis": "C04: M03 §3.2.1; detailed population conditions are internally designed / H08: M19 §19.1.2–19.2.4; internally applied. Reason for application to the harm question: Needed to avoid extending a short study in healthy people to long-term safety during pregnancy/lactation, in children or in older people/those with disease. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review applicability and surveillance scope separately for each population/duration." }, { "item_id": "N34", "question_type": "Diarrhea harm · Was current summary reading distinguished from historical access to original materials?", "question": "Was current summary reading distinguished from historical access to original materials?", "needed": "Original material types, bibliography and access/preservation receipts for each report", "role": "Required", "role_reason": "Needed to avoid upgrading this reading of local materials into a new reading of external full texts/old packages.", "application_exception": "Historical full_text/official PDF/no access/inherited extractions do not represent the actual current read status of each material type.", "criterion": "Separate each report’s physical URL and historical access_level/location from the current unread status of each material type.", "basis": "C03: Data-collection/selection principles in M04 §4.5–4.6; the separation of access from reading and the hyperlink contract are internally designed. Reason for application to the harm question: Needed to avoid upgrading this reading of local materials into a new reading of external full texts/old packages. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare the correspondence between bibliographic URLs and material types with actual reading/attempt events." }, { "item_id": "N35", "question_type": "Diarrhea harm · Are the evidence-review date, access dates and actual server metadata distinguished?", "question": "Are the evidence-review date, access dates and actual server metadata distinguished?", "needed": "Actual access/version dates for each report and original server publication/modification receipts", "role": "Required", "role_reason": "Needed to avoid treating a global date or package metadata as a verified access/original-binary verification date for each report.", "application_exception": "Do not create absent evidence_cutoff/subclaims; retain both the original published/updated metadata and the statement in the text that an actual server publication date is unassigned.", "criterion": "Link the original review reference date, current review date, absence of report-specific access dates and limitations on the server publication date.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material transformation follow the user’s scope and internal design / C03: Data-collection/selection principles in M04 §4.5–4.6; the separation of access from reading and the hyperlink contract are internally designed. Reason for application to the harm question: Needed to avoid treating a global date or package metadata as a verified access/original-binary verification date for each report. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Compare the different date-related events and the meaning of the original metadata." }, { "item_id": "N36", "question_type": "Diarrhea harm · Are gaps in searches, corrections/retractions, unpublished materials and updating identified?", "question": "Are gaps in searches, corrections/retractions, unpublished materials and updating identified?", "needed": "Actual logs of searches/selection, corrections/retractions and registration/unpublished-material checks, and new results", "role": "Required", "role_reason": "Needed to avoid extending a historical self-check into independent review or assurance of worldwide absence of evidence.", "application_exception": "The original package’s statement that search records are preserved does not mean that the complete search logs/ZIP were opened in this review.", "criterion": "Link the limits of self-review/historical access to the scope for updates under the same ID when new evidence/corrections arise.", "basis": "C09: M04 §4.5, §4.6.3; limitations on the current material transformation follow the user’s scope and internal design / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internally applied. Reason for application to the harm question: Needed to avoid extending a historical self-check into independent review or assurance of worldwide absence of evidence. No formal causality/harm grading or clinical certification was performed.", "condition_origin": "These are individual development conditions designed after the current preserved materials had already been read. They adapt the meanings of definitions and are not mechanical copying, blinded development, or clinical preregistration.", "proposed_research": "Review gaps in access/selection and reasons for updates by original ID/version." } ], "language": "en", "translation_date": "2026-11-02" }