{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3102-main", "verdict_number": "3102", "title": "Single-active oral pantothenic acid (vitamin B5) exposure × risk of new or worsened diarrhea adverse events", "view_version": "1.0", "view_created_date": "2026-11-02", "criteria_version": "NGM-v3102-SOLE-ORAL-B5-DIARRHEA-SAFETY-1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Preserved Korean and English manuscripts and case-specific condition and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "External clinical abstracts, full texts, registrations, and analysis plans were not newly read. Historical access records are distinguished from reading the preserved summaries in this review. The original judgments, numerical values, and unverified matters are preserved, and no new search, calculation, or reassessment was performed.", "date_meaning": "This is the date on which the preserved materials were checked, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Adults exposed to oral B5 as the sole active ingredient; the direct data concern healthy adults aged 18–55. Arthritis, pediatric, pregnancy, lactation, and liver or kidney disease populations are not combined as the same population", "intervention": "Pantothenic acid (vitamin B5) as the sole active ingredient; the D-calcium pantothenate salt in the direct exposure data is identified separately · Oral; topical and injected routes excluded · The main study used pantothenic acid tablets distributed by Rugby (as D-calcium pantothenate). Release formulation, additives, and the actual acid/salt mass basis are unverified", "dose": "The stated doses in each study are retained. The paper reports single doses of 500, 1000, 2000, 5000 mg and repeated dosing at 2000 mg/day; no acid/salt conversion or risk-threshold derivation", "comparator": "Comparisons with no exposure, placebo, lower exposure, or other doses are prioritized, but an appropriate comparative estimate of diarrhea risk is unverified. The main study was an uncontrolled open-label trial; redosing after food involved the same people", "endpoint": "Diarrhea adverse events. The main study's MedDRA 21.0 diarrhea category is preserved and is not combined with abdominal pain, nausea, or composite GI symptoms; counts for new versus worsened diarrhea are Not reported", "duration": "Single-dose and 14-day repeated exposures are separated. Follow-up in the main study extended to day 9 for single dosing and day 22 for repeated dosing. The minimum duration associated with risk from long-term or high-dose exposure is unverified", "excluded_extensions": "Other molecules/combination products, other GI endpoints/efficacy, individual incidence/confirmed causality, prevention by taking after food, acid/salt conversion, and minimum risk thresholds/long-term safety are separate boundaries." }, "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.", "current_reports": [], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original question_type is safety, safety_only is true, and grading_status is not_applicable_safety. efficacy_grade/score are not_applicable, and the assessment's efficacy_framework_applied is false. The original grade is ?, score is an empty value, and there are no 7-axis/no_human keys.", "condition_status": "Met", "status_reason": "The condition requiring the safety-only display contract and original values/absences to be preserved unchanged was verified. This does not constitute a judgment of efficacy or individual safety.", "missingness": "The efficacy framework does not apply.", "uncertainty": "The efficacy framework does not apply. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original safety-only display and assessment contract" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The current /ko/effect is the risk of new or worsened diarrhea adverse events. The scope is oral pantothenic acid as the sole active ingredient in adults; abdominal pain, nausea, composite GI symptoms, topical/injected routes, and other molecules/combination products are distinguished.", "condition_status": "Met", "status_reason": "The original question and excluded exposures/outcomes were linked to their designated preserved locations.", "missingness": "The probability of occurrence for an individual across the overall adult population remains separately unverified.", "uncertainty": "The probability of occurrence for an individual across the overall adult population remains separately unverified. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Scope of the original claim/population/exposure/endpoint" }, { "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.", "current_reports": [ "S2404", "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The direct data concern pantothenic acid tablets distributed by Rugby (as D-calcium pantothenate). Other related substances and combination products were not used as direct event evidence for this substance. Batch, purity, additives, and equivalent risk for other salts are unverified.", "condition_status": "Partly verified", "status_reason": "The directly studied substance/distributed product and exclusion boundaries are available, but detailed composition/source/batch have not been established.", "missingness": "Batch, purity, additives, and equivalence of other salts.", "uncertainty": "Batch, purity, additives, and equivalence of other salts. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Identity of the substance/product composition/source ingredients/additives" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The tablet label states pantothenic acid 500 mg (as D-calcium pantothenate), while the dosing table states calcium pantothenate. The pharmacokinetic section refers to 550 mg of calcium salt versus 500 mg of free base in the original text. The actual acid/salt basis and cumulative dose were not converted.", "condition_status": "Partly verified", "status_reason": "The differing descriptions of the stated dose were verified, but the mass basis of the actual clinical dose cannot be established as a single value.", "missingness": "Actual salt amount, acid amount, and purity/cumulative dose.", "uncertainty": "Actual salt amount, acid amount, and purity/cumulative dose. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original tablet label, dosing table, and evidence for the acid/salt mass basis" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The preserved single-dose conditions are 500, 1,000, 2,000, 5,000 mg as reported in the paper. Fasted conditions are distinguished from the subsequent fed condition at 5,000 mg, and the acid/salt basis for each dose remains a separate gap.", "condition_status": "Met", "status_reason": "Only the records of nominal doses by condition were preserved. They were not elevated to verification of actual mass or risk thresholds.", "missingness": "The minimum harmful dose is unverified.", "uncertainty": "The minimum harmful dose is unverified. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Nominal dose and dosing/meal records by condition" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The repeated-dose condition was a nominal 2,000 mg/day for 14 days, and 8 participants completed the repeated-dose part. Follow-up extended to day 9 for single dosing and day 22 for repeated dosing. This record is not long-term exposure data.", "condition_status": "Met", "status_reason": "The preserved exposure/follow-up schedules and the attribution of the repeated-dose denominator were distinguished.", "missingness": "Actual cumulative exposure and adherence for individuals, and long-term harms, are unverified.", "uncertainty": "Actual cumulative exposure and adherence for individuals, and long-term harms, are unverified. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Repeated dosing, adherence, and AE follow-up schedule" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The direct data concern healthy adults aged 18–55. Individual baseline symptoms and the distinction between new onset and worsening of existing diarrhea remain Not reported or Unverified. The detailed sex distribution is also not specified in the current summary.", "condition_status": "Partly verified", "status_reason": "The population category was verified, but detailed baseline diarrhea/selection values cannot be established.", "missingness": "Individual baseline GI, sex/selection, and vulnerability.", "uncertainty": "Individual baseline GI, sex/selection, and vulnerability. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Table of inclusion/exclusion, sex, baseline diarrhea/diseases, and medications" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "Rao is a single-center open-label trial in 40 healthy participants. The single-dose part was completed by 32 participants and the separate repeated-dose part by 8 participants. The diarrhea table for each condition uses a denominator of 8 participants, and the fed condition involved the same 8 participants. The detailed allocation/completion/AE analysis flow is not complete from the current summary alone.", "condition_status": "Partly verified", "status_reason": "Overall/part-specific completion counts and condition denominators are available, but the entire recruitment/missingness/analysis flow cannot be established.", "missingness": "Recruitment/allocation, attrition, and analysis flow for individual conditions.", "uncertainty": "Recruitment/allocation, attrition, and analysis flow for individual conditions. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Recruitment/allocation/exposure/completion/analysis flow and participant linkage by 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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The 5,000 mg single fed dose is a subsequent condition in the same 8 participants after fasted dosing. Washout is described as 2–3 weeks in the main text and summarized as 2 weeks in the abstract. The fixed sequence/meal difference and this difference in descriptions are preserved.", "condition_status": "Conflicting information", "status_reason": "Because the records describe washout at different levels of specificity, they were not replaced with a single confirmed duration. This is a difference in descriptions in the materials, not a new causality judgment.", "missingness": "Actual individual washout schedules and resolution of the difference in descriptions.", "uncertainty": "Actual individual washout schedules and resolution of the difference in descriptions. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original abstract, methods, and individual dosing sequence/washout schedule" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The main study used the MedDRA 21.0 diarrhea category. A diagnostic definition based on stool frequency/form is Not reported or Unverified. GI discomfort or loose stools were not combined into new diarrhea events.", "condition_status": "Partly verified", "status_reason": "The event coding term was verified, but the detailed diagnostic/observation definition has not been established.", "missingness": "Detailed stool frequency/form and diagnostic/coding criteria.", "uncertainty": "Detailed stool frequency/form and diagnostic/coding criteria. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Diarrhea AE definition, coding/diagnostic criteria, and records of stool frequency/form" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original question concerns new or worsened diarrhea. The current preserved summary leaves individual baseline symptoms and counts by new onset/worsening as Not reported or Unverified.", "condition_status": "Unverified", "status_reason": "The question covers both scopes, but data establishing which scope the actual events fall into are unavailable.", "missingness": "Distinction between new/worsened cases and each denominator/person count.", "uncertainty": "Distinction between new/worsened cases and each denominator/person count. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Baseline diarrhea and change criteria, and an AE table separating new/worsened cases" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The preserved summary provides the open-label design and MedDRA diarrhea coding. Diarrhea-specific severity, day of onset, duration, and details of collection procedures are Not reported or Unverified.", "condition_status": "Unverified", "status_reason": "The coding record cannot establish the collection system or diarrhea-specific severity.", "missingness": "Collection methods, severity, and differences in detection.", "uncertainty": "Collection methods, severity, and differences in detection. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "AE collection form/questioning frequency, blinding/ascertainment, and severity table" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The preserved manuscripts kept nausea, vomiting, and abdominal discomfort as separate categories and did not add them to diarrhea. Overall GI discomfort/AE summaries are not added to diarrhea 1/8 or 0/8.", "condition_status": "Met", "status_reason": "The attribution boundary between the selected diarrhea endpoint and other GI categories was maintained.", "missingness": "Detailed values for each other category are not direct estimates in this diarrhea table.", "uncertainty": "Detailed values for each other category are not direct estimates in this diarrhea table. This verification status is limited to the scope of the specific narrow record condition. It does not mean a general incidence rate, individual risk, confirmed causality, prevention by taking after food, absence of risk, or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original AE categories by endpoint and a table of people/events" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "In Table 6, under the paper-labeled 5,000 mg fasted single-dose condition, among 8 participants, 1 reported diarrhea. This is a condition-specific signal observed in a small uncontrolled trial.", "condition_status": "Met", "status_reason": "The retained direct descriptive observation was linked only to the corresponding dose/fasted single-dose condition.", "missingness": "The magnitude of comparative risk increase, general incidence, and causality remain separately unverified.", "uncertainty": "The magnitude of comparative risk increase, general incidence, and causality remain separately unverified. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original Table 6 and the relevant person's AE record" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The 500, 1,000, 2,000 mg fasted single doses and 2,000 mg/day repeated for 14 days each had reports of 0/8 participants. Subsequent fed dosing at 5,000 mg in the same 8 participants was 0/8. All are values collected and reported in a small table, not proof of no risk/prevention by fed dosing.", "condition_status": "Met", "status_reason": "Contrary/no-report records were retained by condition and were not elevated to an effect of 0 or a guarantee of safety.", "missingness": "The actual risk at lower doses/with fed dosing/over the long term is unverified.", "uncertainty": "The actual risk at lower doses/with fed dosing/over the long term is unverified. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Condition-specific Table 6 and the scope of exposure/follow-up and collection" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original record provides condition-specific reports of 1/8 or 0/8 participants and overall/partial completion counts. The number of repeated diarrhea events in the same person, individual exposure/event times, and details of losses from the denominator are not established in the current summary.", "condition_status": "Partly verified", "status_reason": "Condition-specific person denominators are available, but repeated events/person-time and the complete analysis flow are unverified.", "missingness": "Repeated-event counts, person-time, and omissions/missingness.", "uncertainty": "Repeated-event counts, person-time, and omissions/missingness. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Condition-specific person/event counts, follow-up/exposure time, and missing data" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "Rao is an open-label trial without a placebo group or randomized dose assignment. Redosing with food is a subsequent condition in the same people; estimation of diarrhea risk against an appropriate unexposed/placebo comparator is unverified.", "condition_status": "Unverified", "status_reason": "A comparative risk increase cannot be established solely from the uncontrolled/within-person subsequent conditions in the direct data.", "missingness": "Unexposed/placebo risk, background diarrhea rate, and an appropriate comparative estimate.", "uncertainty": "Unexposed/placebo risk, background diarrhea rate, and an appropriate comparative estimate. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Unexposed/appropriate comparator data with matching event definitions/follow-up" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original limitations record leaves diarrhea-specific onset dates and duration as not reported or unverified. Even with a record of AE resolution by the end, diarrhea-specific recovery times and causal clues from dechallenge/rechallenge are not established.", "condition_status": "Unverified", "status_reason": "There is a reported signal after exposure, but no data establishing the diarrhea-specific time course.", "missingness": "Diarrhea-specific onset, duration, recovery, and temporal links.", "uncertainty": "Diarrhea-specific onset, duration, recovery, and temporal links. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Individual logs of dosing, blood sampling/meals, and diarrhea onset/recovery" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The investigator considered the diarrhea at least possibly related. The original safety assessment retains the signal and Caution conclusion, but comparative risk and the contribution of alternative causes such as excipients, infection, and diet are unverified. This table does not create a new causality judgment or score.", "condition_status": "Partly verified", "status_reason": "The qualitative signal conclusion was verified, but established causality for individual diarrhea was not verified.", "missingness": "Individual evidence of relatedness, alternative causes, and comparative risk.", "uncertainty": "Individual evidence of relatedness, alternative causes, and comparative risk. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "The basis for individual AE relatedness assessments and records of 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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "Rao prohibited other medications and supplements but did not control dietary pantothenic acid intake. The contributions of excipients, infection, diet, and individual susceptibility are unverified.", "condition_status": "Partly verified", "status_reason": "There were some restrictions on concurrent exposures, but no data ruling out all alternative explanations.", "missingness": "Contributions of diet, excipients, infection, and individual susceptibility.", "uncertainty": "Contributions of diet, excipients, infection, and individual susceptibility. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Records of medications/supplements, diet, meals, excipients, and infection/baseline symptoms" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The main study reports no deaths, serious adverse events, or discontinuations due to adverse events. In contrast to the completion records for 32 single-dose participants and 8 repeated-dose participants, the detailed flow of diarrhea-specific noncollection/missingness is not established in the current summary.", "condition_status": "Partly verified", "status_reason": "A general safety summary and completion counts are available, but the complete diarrhea-specific flow and presence or absence of omissions are unverified.", "missingness": "Diarrhea-specific discontinuations and missingness/noncollection flow.", "uncertainty": "Diarrhea-specific discontinuations and missingness/noncollection flow. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Diarrhea-specific reasons for discontinuation/dropout, periods without collection, and participant flow" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original record leaves registration, protocol, and statistical analysis plan unverified and does not conclude that preregistration was absent. Records of registration/some metadata access failures at that time are also not actual access failures in this work.", "condition_status": "Unverified", "status_reason": "The current archived summaries alone cannot establish prespecification/changes or the scope of selective reporting.", "missingness": "Registration/plans, prespecification, and changes/selective reporting.", "uncertainty": "Registration/plans, prespecification, and changes/selective reporting. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Registration, protocol, SAP, and records of diarrhea prespecification/changes" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The retained manuscript left comparative risk estimates, the background diarrhea rate, and the minimum harmful dose/duration unverified. Risk differences, risk ratios, incidence rates, CIs, P values, and NNH were not derived, and this table does not calculate them either.", "condition_status": "Unverified", "status_reason": "There are no data establishing quantitative comparative risk or harm criteria beyond the descriptive observations of 1/8 and 0/8.", "missingness": "Formal comparative estimates, CIs, background risk, and clinical criteria.", "uncertainty": "Formal comparative estimates, CIs, background risk, and clinical criteria. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original comparative estimates, denominators, CIs/uncertainty, and clinical harm criteria" }, { "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.", "current_reports": [ "S2402", "S2405" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The arthritis trial summarized by SCF escalated calcium pantothenate over 8 weeks and states that no treatment side effects were recorded. The original diarrhea event table was not acquired/unverified, so this was not converted into 0 diarrhea events or an established safety denominator. S2405 is a PubMed bibliographic record without an abstract.", "condition_status": "Partly verified", "status_reason": "Contrary general AE context and bibliographic information are available, but the original diarrhea-specific results and collection methods are unverified.", "missingness": "The original GPRG event table, diarrhea definition/collection, and denominator.", "uncertainty": "The original GPRG event table, diarrhea definition/collection, and denominator. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "The original GPRG diarrhea/AE event table and dosing, population, and collection methods" }, { "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.", "current_reports": [ "S2402", "S2405" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "In the GPRG record, the narrative total of 94 participants is inconsistent with the arm-specific counts of 47 and 46 participants (a total of 93 participants in the original record). The conflict was retained, and neither value was selected as an established diarrhea analysis denominator in this table.", "condition_status": "Conflicting information", "status_reason": "The inconsistent original descriptions of the same total were made explicit, and no new arithmetic/denominator correction was made.", "missingness": "Actual definitions of the total, allocation/completion, and analysis denominators.", "uncertainty": "Actual definitions of the total, allocation/completion, and analysis denominators. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original participant flow, arm-specific allocation/analysis tables, and SCF's cited statement" }, { "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.", "current_reports": [ "S06" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The reused NIH S06 gives 10 g/day as an example of very high intake and mentions the possibility of mild diarrhea and GI discomfort. The exact number of cases, denominator, salt, and duration were not verified in this extraction. It is not a newly validated event rate, toxicity threshold, upper intake level, or individual recommended intake.", "condition_status": "Partly verified", "status_reason": "A retained qualitative example is available, but the identity of the original events and their denominator/exposure scope are unverified.", "missingness": "Underlying cases, denominator, and exact formulation/duration.", "uncertainty": "Underlying cases, denominator, and exact formulation/duration. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "The relevant NIH section and underlying original cases and exposure/event data" }, { "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.", "current_reports": [ "S06", "S2402", "S2406" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "S06, S2402, and S2406 are official/expert summary lineages of historical high-dose observations. The duration, exact formulation, and event counts/denominators in the 10–20 g/day reports are unverified. Do not count LEGACY-HIGH-DOSE-SUMMARY as one established human trial or three independent replications.", "condition_status": "Partly verified", "status_reason": "The overlapping summary lineages and limitations were verified, but the independence of the underlying original cases is not established.", "missingness": "Original case identities, overlap/independence, and actual events/exposures.", "uncertainty": "Original case identities, overlap/independence, and actual events/exposures. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "SCF/CIR citation lineage, Elder 1987, and underlying original cases" }, { "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.", "current_reports": [ "S2401", "S2403" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "FNB 1998 states that an upper intake level could not be established because reports of harm were not found. The checked EFSA version 11(2025-08) also indicates that an upper intake level for pantothenic acid could not be derived because of insufficient data. This does not mean unlimited safety or a legally permitted therapeutic dose.", "condition_status": "Met", "status_reason": "The retained editions and interpretation of insufficient data were linked as they stood, and no new safety/regulatory judgment was made.", "missingness": "Current official editions/regulatory changes were not looked up in this work.", "uncertainty": "Current official editions/regulatory changes were not looked up in this work. This verification status is limited to the scope of the narrow record condition concerned. It does not mean general incidence, individual risk, established causality, prevention by fed dosing, absence of risk, or absence of research worldwide.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "The relevant official edition/harm assessment section and the basis for data insufficiency" }, { "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.", "current_reports": [ "S06" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The reused US adequate intakes are 5 mg/day for adults, 6 mg/day during pregnancy and 7 mg/day during lactation. These indicate nutritional adequacy, not a diarrhea threshold or high-dose treatment instructions. Do not pool food intake and high-dose single-active-ingredient exposure into the same dose group.", "condition_status": "Met", "status_reason": "The condition distinguishing the roles of AI values and clinical high-dose exposures was verified.", "missingness": "These nutritional references cannot determine an individual’s probability of diarrhea/treatment dose.", "uncertainty": "These nutritional references cannot determine an individual’s probability of diarrhea/treatment dose. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Populations/definitions of nutritional reference values and data on high-dose preparations" }, { "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.", "current_reports": [ "S2406" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "S2406 is a safety review of the cosmetic use of panthenol, pantothenic acid and their derivatives. In the current evidence, it is used as a qualitative summary of historical high-dose oral observations, not converted into authorization or safety certification of single-active oral B5.", "condition_status": "Met", "status_reason": "The material’s actual title/review scope was distinguished from its citation role in this table.", "missingness": "Oral-product authorization and individual safety judgments are not outcomes of this review.", "uncertainty": "Oral-product authorization and individual safety judgments are not outcomes of this review. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "CIR review scope, toxicology section and underlying oral-use references" }, { "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.", "current_reports": [ "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "Evans S2407 is excluded because pantethine is a different molecule. Yang S2408 provides product-level tolerability with unestablished monotherapy composition, so it is not transferred to the risk of single-active pantothenic acid. Not applicable for each n is a value indicating the exclusion role.", "condition_status": "Met", "status_reason": "The distinct reasons for the two current exclusions and the meaning of the denominator’s non-applicability were retained.", "missingness": "The old separate extractions/PMC full texts and composition were not newly read in this review.", "uncertainty": "The old separate extractions/PMC full texts and composition were not newly read in this review. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Identity of the product’s ingredients/formulation and historical exclusion extraction" }, { "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.", "current_reports": [ "S2404", "S2405", "S2406", "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "Rao disclosed support from CoA Therapeutics and employment, consultancy and shareholdings related to development companies. Funding for the historical underlying cases is unverified, while the CIR/Personal Care Products Council support for CIR 2022 funds that review. Funding for the arthritis/excluded materials also remains unverified.", "condition_status": "Partly verified", "status_reason": "Relationships have been disclosed for the main study/review, but support for the underlying cases and other families is not established.", "missingness": "Funding/product provision for underlying cases and arthritis/excluded families.", "uncertainty": "Funding/product provision for underlying cases and arthritis/excluded families. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original Funding/COI, support/product provision and funding records for underlying cases" }, { "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.", "current_reports": [ "S2404" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The direct evidence concerns healthy people aged 18–55 undergoing single-dose or 14-day repeated exposure. Direct diarrhea risks during pregnancy/lactation, in children, older people, those with liver/kidney disease and during long-term exposure are unverified.", "condition_status": "Unverified", "status_reason": "There are no data establishing harms outside the population/duration of the direct study.", "missingness": "Direct harm/denominators/duration for long-term exposure and vulnerable populations.", "uncertainty": "Direct harm/denominators/duration for long-term exposure and vulnerable populations. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Long-term follow-up and direct diarrhea/exposure/comparator data by population" }, { "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.", "current_reports": [ "S06", "S2401", "S2402", "S2403", "S2404", "S2405", "S2406", "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The actual current input is an archived summary preserving the KO/EN manuscripts, 5 evidence groups, 9 bibliographic records and assessment/metadata. All external original texts/registrations/official documents and old separate extractions were not attempted, acquired or read in this review. Historical access levels are retained only in separate fields.", "condition_status": "Met", "status_reason": "Current local-summary reading was recorded separately from the historical/current external access for the 9 reports.", "missingness": "No current comparison against external original materials was performed.", "uncertainty": "No current comparison against external original materials was performed. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Original material types, bibliography and access/preservation receipts for each report" }, { "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.", "current_reports": [ "S06", "S2401", "S2402", "S2403", "S2404", "S2405", "S2406", "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original content reference date/verified_date is 2026-09-15, and the local review date recorded here is 2026-10-05. Each bibliographic record lacks an access-date key, so historical_access_date is empty. The original published/updated values are preserved, while the text states that an actual server publication date is unassigned. The evidence_cutoff and subclaims keys are also absent.", "condition_status": "Met", "status_reason": "The record condition separating dates, absences and historical metadata by event was verified.", "missingness": "Actual access dates for each report, the actual server publication date and original-binary SHA were not newly verified.", "uncertainty": "Actual access dates for each report, the actual server publication date and original-binary SHA were not newly verified. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Actual access/version dates for each report and original server publication/modification receipts" }, { "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.", "current_reports": [ "S06", "S2401", "S2402", "S2403", "S2404", "S2405", "S2406", "S2407", "S2408" ], "existence": "Limited to the currently preserved manuscripts, structure/bibliography, and explicitly stated unverified matters and historical access scope.", "acquired_read": "Summary read: The specified literals in the preserved manuscripts were actually read. External material types were not attempted, acquired, or read in this review.", "observation": "The original review was a single-assistant self-review, with registration/some metadata-access failures remaining. It is not an independent external review or assurance that no corrections, retractions or unpublished materials exist. New comparative safety evidence, salt/labeled-dose information, corrections/regulatory changes or numerical/classification errors are reasons to update dates/history under the same ID/URL after assignment.", "condition_status": "Unverified", "status_reason": "Updating principles exist, but search completeness and the current scope of corrections/unpublished materials were not checked in this review.", "missingness": "Search/access completeness and the current scope of corrections/retractions/unpublished materials.", "uncertainty": "Search/access completeness and the current scope of corrections/retractions/unpublished materials. This verification state is limited to the scope of the specific narrow record condition. It does not imply general incidence, individual risk, definitive causality, prevention under fed conditions, no risk or worldwide absence of research.", "review_date": "2026-10-05", "reading_status": "Original source Not read · Preserved summary read", "additional_material": "Actual logs of searches/selection, corrections/retractions and registration/unpublished-material checks, and new results" } ], "reports": [ { "report_id": "S06", "title": "NIH Office of Dietary Supplements. Pantothenic Acid — Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/", "report_type": "Official NIH web explanation · historical reuse", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at preservation: The reused NIH material mentions possible mild diarrhea/GI distress with very high intake of 10 g/day. The original case count, denominator, salt and duration are unverified in this extraction. Adult/pregnancy/lactation AI values of 5/6/7 mg/day are nutritional adequacy references, not diarrhea thresholds or dosing instructions.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official NIH web full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: full_text. Historical location in the reference bibliography: Table 1; Health Risks from Excessive Pantothenic Acid; Interactions with Medications Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S06-M1", "url": "https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/", "parent_url": null }, { "material_type": "Underlying oral-exposure cases/original event data", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Table 1; Health Risks from Excessive Pantothenic Acid; Interactions with Medications Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S06-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/PantothenicAcid-HealthProfessional/" } ] }, { "report_id": "S2401", "title": "Institute of Medicine (1998), Dietary Reference Intakes, chapter 10: Pantothenic Acid", "url": "https://www.nationalacademies.org/read/6015/chapter/12", "report_type": "Official DRI assessment HTML · historical access", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at preservation: The US FNB 1998 states that it could not set an upper limit because it had not found reports of adverse effects. This statement of insufficient data is not interpreted as unlimited safety or a legally permitted treatment dose.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official DRI HTML assessment section", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: official_full_html. Historical location in the reference bibliography: Printed pp. 370-371: Tolerable Upper Intake Levels / Hazard Identification / Risk Characterization Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2401-M1", "url": "https://www.nationalacademies.org/read/6015/chapter/12", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.nationalacademies.org/read/6015/chapter/12" } ] }, { "report_id": "S2402", "title": "Scientific Committee on Food (2002), Tolerable Upper Intake Level of Pantothenic Acid, reprinted in 2006 compilation", "url": "https://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf", "report_type": "Official SCF assessment PDF · historical access", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at preservation: SCF summarizes the absence of recorded treatment side effects in an 8-week dose-escalation arthritis trial. The original diarrhea-event table has not been acquired, and the conflict between a narrative total of 94 people and 47/46 people (an original-record total of 93 people) is retained. Historical reports of 10–20 g/day are used only as a qualitative evidence lineage with unverified exact formulations, durations and event counts/denominators.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official SCF PDF assessment", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: official_pdf_text_and_screenshot. Historical location in the reference bibliography: Pantothenic Acid: printed pp. 118-119, PDF pages 120-121; sections 3.2, 4, 5, 6 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2402-M1", "url": "https://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf", "parent_url": null }, { "material_type": "GPRG original paper/diarrhea-event table", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Pantothenic Acid: printed pp. 118-119, PDF pages 120-121; sections 3.2, 4, 5, 6 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2402-M2", "url": null, "parent_url": null }, { "material_type": "Historical original high-dose cases", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Pantothenic Acid: printed pp. 118-119, PDF pages 120-121; sections 3.2, 4, 5, 6 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2402-M3", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.efsa.europa.eu/sites/default/files/efsa_rep/blobserver_assets/ndatolerableuil.pdf" } ] }, { "report_id": "S2403", "title": "EFSA, Summary of Tolerable Upper Intake Levels, version 11 (August 2025)", "url": "https://www.efsa.europa.eu/sites/default/files/2024-05/ul-summary-report.pdf", "report_type": "Official EFSA UL summary PDF · historical access", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at preservation: The inspected version 11 (2025-08) table indicates insufficient data to derive a pantothenic acid upper limit. The URL’s 2024-05 path is not converted into an actual version date, and the latest version/regulatory changes were not looked up in this review.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official EFSA UL summary PDF", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: official_pdf_text_and_screenshot. Historical location in the reference bibliography: Cover version/date; p. 4 Table 3, Pantothenic acid row Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2403-M1", "url": "https://www.efsa.europa.eu/sites/default/files/2024-05/ul-summary-report.pdf", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.efsa.europa.eu/sites/default/files/2024-05/ul-summary-report.pdf" } ] }, { "report_id": "S2404", "title": "Rao SI et al. (2021). The Pharmacokinetics of Orally Administered Calcium Pantothenate in Healthy Adults", "url": "https://www.gavinpublishers.com/article/view/the-pharmacokinetics-of-orally-administered-calcium-pantothenate-in-healthy-adults", "report_type": "Original-paper HTML; historical access to PDF tables is separate", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": "RAO-2021-PK", "independent_replication": null, "observed_result": "Record at preservation: In an open-label study of healthy people aged 18–55, 40 participants were included; 32 completed the single-dose part and 8 the repeated-dose part. The paper-labeled 5,000 mg fasted single-dose result of 1/8 people and, in the same 8 people, the subsequent fed result of 0/8 people are preserved. The 500/1,000/2,000 mg fasted single-dose conditions and 2,000 mg/day repeated for 14 days each yielded 0/8. These are MedDRA 21.0 diarrhea observations; other GI items are not added. Single-dose follow-up through Day 9/repeated-dose follow-up through Day 22, the methods’ 2–3-week versus the abstract’s 2-week washout descriptions and the limitations of acid/salt labeling are retained. The investigator’s possible-relatedness attribution and the record that all AE had resolved at the end do not establish a diarrhea-specific recovery date/definitive causality. The absence of placebo/randomized allocation, uncontrolled dietary B5 and CoA support/employment/consultancy/shareholdings are preserved. No new comparative risk, incidence, preventive effect of fed dosing or long-term safety conclusion is established.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Original-paper HTML full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The original citation’s primary_full_html_and_pdf_screenshots is metadata combining HTML access and screenshots of numerical PDF tables. This row is limited to the HTML portion and does not indicate external reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Original-paper HTML full text (historical record of the HTML portion of the original access_level). Historical location in the reference bibliography: Methods pp. 2-3; Safety pp. 6-7; Table 6 pp. 7-8; Conflict of Interest p. 9 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2404-M1", "url": "https://www.gavinpublishers.com/article/view/the-pharmacokinetics-of-orally-administered-calcium-pantothenate-in-healthy-adults", "parent_url": null }, { "material_type": "Original-paper PDF full text/original Table 6", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The original citation records access to screenshots of numerical PDF tables. This is not expanded into verified access to the full PDF or individual AE/registration/plans. The original metadata are retained in contextual_document_access_level. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Original-paper PDF numerical-table screenshots (historical record; reading of the entire PDF full text is unverified). Historical location in the reference bibliography: Methods pp. 2-3; Safety pp. 6-7; Table 6 pp. 7-8; Conflict of Interest p. 9 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2404-M2", "url": null, "parent_url": null }, { "material_type": "Individual AE/exposure data and appendices", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Methods pp. 2-3; Safety pp. 6-7; Table 6 pp. 7-8; Conflict of Interest p. 9 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2404-M3", "url": null, "parent_url": null }, { "material_type": "Registration/protocol/SAP", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Methods pp. 2-3; Safety pp. 6-7; Table 6 pp. 7-8; Conflict of Interest p. 9 Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2404-M4", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.gavinpublishers.com/article/view/the-pharmacokinetics-of-orally-administered-calcium-pantothenate-in-healthy-adults" } ] }, { "report_id": "S2405", "title": "Calcium pantothenate in arthritic conditions. A report from the General Practitioner Research Group (1980)", "url": "https://pubmed.ncbi.nlm.nih.gov/6988826/", "report_type": "PubMed bibliography without an abstract; historical non-acquisition of the original paper", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": "GPRG-1980-ARTHRITIS", "independent_replication": null, "observed_result": "Record at preservation: The retained historical access concerns the title/journal and no-abstract bibliographic record for PMID 6988826. Clinical content is limited to the SCF 2nd-hand summary’s 8-week dose escalation, absence of recorded general treatment side effects and the conflict between 94 people and group counts of 47/46. Do not claim that the original diarrhea-event table was acquired/read or convert this into 0 diarrhea events.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic page without an abstract", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: primary_metadata_no_abstract. Historical location in the reference bibliography: PubMed title / PMID / journal: Practitioner 1980;224(1340):208-211; No abstract available Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2405-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/6988826/", "parent_url": null }, { "material_type": "GPRG original-paper full text/diarrhea-event table", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: PubMed title / PMID / journal: Practitioner 1980;224(1340):208-211; No abstract available Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2405-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/6988826/" } ] }, { "report_id": "S2406", "title": "Scott LN et al. (2022). Safety Assessment of Panthenol, Pantothenic Acid, and Derivatives as Used in Cosmetics", "url": "https://journals.sagepub.com/doi/10.1177/10915818221124809", "report_type": "CIR cosmetic-review HTML · historical access", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": null, "independent_replication": null, "observed_result": "Record at preservation: Scott 2022 is a review of the safety of panthenol, pantothenic acid and their derivatives in cosmetic use. Historical high-dose oral summaries, including Elder 1987, are limited to qualitative signals at 10–20 g/day; exact formulations, durations and event counts/denominators are unverified. CIR/Personal Care Products Council support funds this review, while funding for the underlying cases is unverified. It is not counted as authorization/safety certification of oral preparations or independent human replication.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "CIR review HTML full text", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: full_html. Historical location in the reference bibliography: Toxicological Studies first paragraph; reference 4 (Elder 1987); Funding and conflicts Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2406-M1", "url": "https://journals.sagepub.com/doi/10.1177/10915818221124809", "parent_url": null }, { "material_type": "Elder 1987 and underlying original cases", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: Toxicological Studies first paragraph; reference 4 (Elder 1987); Funding and conflicts Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2406-M2", "url": null, "parent_url": null } ], "links": [ { "label": "Source", "url": "https://journals.sagepub.com/doi/10.1177/10915818221124809" } ] }, { "report_id": "S2407", "title": "Evans et al. pantethine lipid trial, prior package exclusion record", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3942300/", "report_type": "Exclusion extraction from an old package; the PMC link provides reference identity", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": "EVANS-PANTETHINE-EXCLUDED", "independent_replication": null, "observed_result": "Record at preservation: The preserved old extraction classifies this as a pantethine trial and does not attribute it to diarrhea from single-active pantothenic acid. Not applicable for n indicates the exclusion role and does not mean 0 people/no risk. The old separate file and PMC full text were not read in this review.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Original file of the old package’s exclusion extraction", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: provided_prior_package_extraction. Historical location in the reference bibliography: reference/reused_TASK0022.json and legacy_366.json: pantethine, not pantothenic acid Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2407-M1", "url": null, "parent_url": null }, { "material_type": "PMC original-paper link (current reference identity)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: reference/reused_TASK0022.json and legacy_366.json: pantethine, not pantothenic acid Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2407-M2", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3942300/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3942300/" } ] }, { "report_id": "S2408", "title": "Pantothenic-acid-based acne product, prior package composition assessment", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4065280/", "report_type": "Composition assessment from an old package; the PMC link provides reference identity", "existence": "A reference to archived bibliography/historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean/English summaries and bibliographic records in the archived manuscripts were read. The linked external original materials were not read in this review.", "study_family": "YANG-2014-EXCLUDED", "independent_replication": null, "observed_result": "Record at preservation: Because monotherapy composition is unestablished in the preserved acne-product extraction, product-level tolerability is not transferred to the risk of single-active pantothenic acid. Not applicable for n indicates the exclusion role, not 0 people. The old separate composition file and PMC full text were not read in this review.", "result_level": "This is content recorded in the archived manuscripts, not the result of a new comparison against current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Original file of the old package’s composition assessment", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. Only the historical scope pertaining to this document/extraction itself in the preserved citation is retained. It is not inherited by other underlying original materials or treated as actual full-text reading in this review. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: provided_prior_package_extraction. Historical location in the reference bibliography: reference/reused_TASK0021.json: trial-product monotherapy not established Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2408-M1", "url": null, "parent_url": null }, { "material_type": "PMC original-paper link (current reference identity)", "public_status": "Unverified (no external lookup in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-02", "qualification": "This is preserved historical identity/access information or a required material type. Its external existence/availability was not newly checked in this review. What was actually read was the relevant manuscript, evidence and bibliography in the currently preserved source archive summary. This external original text/old separate file was not read in this review. The historical access level of this original material itself is unverified in the current source. contextual_document_access_level is the original access metadata of the containing document/inherited extraction that mentions it; it is not inherited as full-text access to this original material. Historical access dates for each material are unverified. The archived manuscript’s review date of 2026-09-15 is not the access date of this original-material file. Historical access level of this material itself: Unverified. Historical location in the reference bibliography: reference/reused_TASK0021.json: trial-product monotherapy not established Bibliographic access records are not inherited as access to separate full texts/underlying materials. This does not mean that external original materials were acquired or full texts read in this review.", "material_id": "S2408-M2", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4065280/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4065280/" } ] } ], "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." }, "study_overlap": { "state": "The 5 archived evidence lineages do not represent a count of independent clinical trials or a total number of participants. RAO-2021-PK (S2404): used for the direct signal and descriptive statistics; not used for randomized/placebo comparative-risk estimates or general incidence / GPRG-1980-ARTHRITIS (S2405, S2402): counter/contextual evidence / LEGACY-HIGH-DOSE-SUMMARY (S06, S2402, S2406): used only for qualitative high-dose safety signals; review lineages are not summed as independent replications / EVANS-PANTETHINE-EXCLUDED (S2407): excluded / YANG-2014-EXCLUDED (S2408): excluded. Repeated citations of the same study and overlapping high-dose summaries are not summed as independent replications.", "unique_trial_count": null, "unique_participant_count": null, "reason": "The 5 archived evidence lineages do not represent a count of independent clinical trials or a total number of participants. RAO-2021-PK (S2404): used for the direct signal and descriptive statistics; not used for randomized/placebo comparative-risk estimates or general incidence / GPRG-1980-ARTHRITIS (S2405, S2402): counter/contextual evidence / LEGACY-HIGH-DOSE-SUMMARY (S06, S2402, S2406): used only for qualitative high-dose safety signals; review lineages are not summed as independent replications / EVANS-PANTETHINE-EXCLUDED (S2407): excluded / YANG-2014-EXCLUDED (S2408): excluded. Repeated citations of the same study and overlapping high-dose summaries are not summed as independent replications." }, "history": [ { "date": "2026-11-02", "kind": "Public display/material separation", "view_version": "1.0", "change": "The public display/materials were prepared from the existing 36 items. No new clinical search, verification-state change or scoring was performed." } ], "safety_scope": { "question_type": "safety", "deliverable_kind": "safety_brief", "safety_only": true, "grading_status": "not_applicable_safety", "efficacy_grade": "not_applicable", "efficacy_score": "not_applicable", "efficacy_framework_applied": false, "forbid_efficacy_badge": true, "forbid_aggregate_rating": true, "warning": "Caution", "meaning": "This is a safety-only review. Item verification states indicate the scope of verification of archived materials and question boundaries; they do not represent efficacy grades, guarantees of individual safety or probabilities of occurrence." }, "reader_labels": { "independent_replication_unverified": "Independent replication is unverified." }, "language": "en", "translation_date": "2026-11-02" }