{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3083-main", "verdict_number": "3083", "title": "Nicotinic acid (prescription NIASPAN extended-release tablets) × Mean LDL-C percentage change in primary hypercholesterolaemia", "view_version": "1.0", "view_created_date": "2026-10-29", "criteria_version": "1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-14", "review_scope": { "materials_read": "Retained Korean/English summaries and case-specific condition/application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Prepared from retained review summaries and condition-application records. External PDFs, abstracts, full texts and registration were not read in this work. This is not current independent clinical verification or official methodological certification.", "date_meaning": "The date retained material was checked, not the date of a latest clinical-literature search." }, "claim_context": { "population": "Primary hypercholesterolaemia with LDL-C >160 mg/dL despite dietary management. This is distinct from deficiency correction and an add-on statin strategy.", "intervention": "Nicotinic acid (prescription NIASPAN extended-release tablets); NIASPAN nicotinic acid extended-release tablets, distinct from nicotinamide and inositol hexanicotinate; oral", "dose": "Key contrast: 2000 mg/day; other arms in the same trial, including 1000 mg/day, are supporting records and are not averaged together.", "comparator": "Matched placebo on the same dietary-treatment background. Compare the key fixed dose of 2000 mg with contemporaneous placebo; do not mix in other times from the dose-escalation table.", "endpoint": "Mean LDL-C percentage change from baseline at 16 weeks in regulatory Table 3. The article abstract alone does not verify agreement with an originally registered 1st (primary) endpoint.", "duration": "Regulatory table: 16 weeks including 4-week titration. The publisher abstract describes 12 weeks of treatment; retain both definitions.", "excluded_extensions": [ "Deficiency correction, add-on statin TG strategies and other vitamin B3 formulations", "Extensions to myocardial infarction, mortality, optimal dose, long-term effects or subgroups" ] }, "requirements": [ { "item_id": "N01", "question_type": "Separate question", "question": "Which NIASPAN LDL-C contrast is retained?", "needed": "Exact locations for the assessed claim, claim conditions and editorial scope, and the canonical URL.", "role": "Required", "role_reason": "Needed to keep this LDL-C marker question separate from the full original multi-lipid assessment.", "application_exception": "The subclaim array is empty. Do not automatically generate tables for other doses/endpoints or rewrite 128/2346.", "criterion": "Connect the exact assessed claim, formulation, population, diet plus placebo, 2000 mg/day and 16 weeks including titration as one question.", "basis": "M03 §3.1, §3.2.1–3.2.4: question-clarification principles; detailed separation rules are locally designed; M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed — case-specific adaptation for the separate question.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "First fix the question and report-eligibility table, then check whether other formulations, TG or clinical-event questions have entered the scope.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The assessed claim is mean LDL-C percentage change in primary hypercholesterolaemia, limited to oral NIASPAN nicotinic acid extended-release tablets at 2000 mg/day versus diet plus placebo over 16 weeks including titration.", "condition_status": "Met", "status_reason": "The exact assessed claim, claim conditions and editorial scope support this single question.", "missingness": "The earlier review verified this claim identity and scope in retained material and recorded that new checking of external originals and website publication had not been performed at that time.", "uncertainty": "The earlier review verified this claim identity and scope in retained material and recorded that new checking of external originals and website publication had not been performed at that time.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Exact locations for the assessed claim, claim conditions and editorial scope, and the canonical URL." }, { "item_id": "N02", "question_type": "Population and selection", "question": "Are eligibility criteria and baseline characteristics verified?", "needed": "The original article’s inclusion/exclusion criteria, age, baseline table and preceding dietary procedures.", "role": "Required", "role_reason": "Needed to avoid transferring results in a high-LDL population to all adults, CKD or add-on statin strategies.", "application_exception": "Distinguish the planned adult-population question from unverified age/comorbidity details; do not establish a failure of representativeness.", "criterion": "Connect primary hypercholesterolaemia with LDL-C >160 mg/dL despite dietary management to actual eligibility and baseline characteristics.", "basis": "M03 §3.2.1: detailed population conditions are locally designed; M08 §8.1–8.2.3: local application — case-specific adaptation for population and selection.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Check recruitment criteria and baseline tables against the target and included populations, including selection limitations.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The population has primary hypercholesterolaemia with LDL-C >160 mg/dL despite dietary management. Retained summaries distinguish this from deficiency correction and add-on statin strategies, but the retained abstract/regulatory-table summaries do not verify detailed eligibility or baseline tables.", "condition_status": "Partly verified", "status_reason": "The diagnosis and LDL entry criterion are stated; detailed recruitment and baseline composition remain unresolved.", "missingness": "Detailed age, comorbidities, eligibility and baseline balance between arms are unverified.", "uncertainty": "Detailed age, comorbidities, eligibility and baseline balance between arms are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The original article’s inclusion/exclusion criteria, age, baseline table and preceding dietary procedures." }, { "item_id": "N03", "question_type": "Nutritional status", "question": "Does this trial concern correction of B3 deficiency?", "needed": "Deficiency-based selection, baseline B3 concentrations and eligibility definitions.", "role": "Required (population boundary)", "role_reason": "Needed to distinguish nutritional-deficiency treatment from lipid changes at pharmacological doses.", "application_exception": "Unreported B3 concentrations do not establish laboratory-confirmed absence of deficiency. Do not require concentration measurement unconditionally for the narrow lipid question.", "criterion": "Distinguish a trial not selected for deficiency from the limited scope of unreported B3 concentrations in the abstract/tables.", "basis": "M03 §3.2.1: detailed population conditions are locally designed; M03 §3.2.1–3.2.4: dose, duration and effect-modification details are locally designed — case-specific adaptation for nutritional status.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Check whether original recruitment criteria required deficiency; do not pool deficiency-correction evidence as a high-LDL treatment effect.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The retained record states that the trial did not select nutritional deficiency and that the abstract/tables used contained no diagnostic B3 concentration data.", "condition_status": "Met", "status_reason": "The non-deficiency selection boundary and the limited concentration-reporting scope were verified.", "missingness": "The scope was verified as a trial not selected for deficiency. Individual B3 deficiency status and baseline concentrations were not verified.", "uncertainty": "The scope was verified as a trial not selected for deficiency. Individual B3 deficiency status and baseline concentrations were not verified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Deficiency-based selection, baseline B3 concentrations and eligibility definitions." }, { "item_id": "N04", "question_type": "Ingredient and formulation", "question": "What are the selected ingredient, formulation and route?", "needed": "Original labelling and product identity for NIASPAN ingredient, ER formulation and oral route.", "role": "Required", "role_reason": "Needed to avoid assigning the same effects/harms to other molecules or release formulations.", "application_exception": "Do not combine general vitamin B3, inositol hexanicotinate, nicotinamide or other formulations as direct evidence.", "criterion": "Distinguish oral NIASPAN nicotinic acid extended-release tablets from other B3 forms.", "basis": "M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed — case-specific adaptation for ingredient and formulation.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link product/formulation definitions to result tables and exclude interchange at the same mg dose with immediate-release, sustained-release, no-flush products or nicotinamide.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original records identify oral NIASPAN nicotinic acid extended-release and record that other niacin forms are not equivalent.", "condition_status": "Met", "status_reason": "Retained ingredient, formulation and route identities agree.", "missingness": "This product/route boundary was verified. Current physical labelling, product approval and manufacturing origin were not newly verified.", "uncertainty": "This product/route boundary was verified. Current physical labelling, product approval and manufacturing origin were not newly verified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original labelling and product identity for NIASPAN ingredient, ER formulation and oral route." }, { "item_id": "N05", "question_type": "Dose and actual exposure", "question": "Are the target dose, titration and actual administration history verified?", "needed": "Arm-specific titration schedules, administration/stopping histories and actual doses.", "role": "Required", "role_reason": "Needed to avoid treating the target 2000 mg as actual exposure throughout the entire period.", "application_exception": "The 1000 mg arm in the same trial is a supporting record; do not create a pooled mean dose.", "criterion": "Distinguish the target 2000 mg/day, 4-week titration and actual administration/adherence.", "basis": "M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed; M03 §3.2.3, M08 §8.2.2–8.2.3: local application — case-specific adaptation for dose and actual exposure.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Reconstruct exposure during titration and maintenance, then compare actual doses and deviations with intended prescribing.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The key contrast is 2000 mg/day and the label period includes 4-week titration. A 1000 mg arm is also present, but detailed titration and administration histories are unconfirmed.", "condition_status": "Partly verified", "status_reason": "The target dose and titration-inclusive definition were verified; detailed actual exposure is unavailable.", "missingness": "Doses at each titration visit, adherence and actual cumulative exposure are unverified.", "uncertainty": "Doses at each titration visit, adherence and actual cumulative exposure are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific titration schedules, administration/stopping histories and actual doses." }, { "item_id": "N06", "question_type": "Comparator strategy", "question": "What is the main comparator strategy?", "needed": "The common dietary treatment, placebo composition and contemporaneous Table 3 comparison.", "role": "Required", "role_reason": "The comparison must retain the same time/background to preserve attribution of the LDL-C difference.", "application_exception": "Do not substitute AIM-HIGH’s low-dose IR control or statin ± ezetimibe strategy for this placebo.", "criterion": "Connect contemporaneous 2000 mg and placebo arms on the same dietary background.", "basis": "M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed; M03 §3.2.3, M08 §8.2.2–8.2.3: local application — case-specific adaptation for comparator strategy.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare intervention/control strategies and exclude add-on statin TG strategies and other times in the dose-escalation table.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The selected comparator is matched placebo on the same dietary-treatment background. Use the contemporaneous fixed-dose comparison in Table 3, without mixing the dose-escalation table at other times.", "condition_status": "Met", "status_reason": "The comparator conditions and the current article/regulatory-table comparison scope are explicit.", "missingness": "The main comparator strategy was verified. Detailed dietary adherence and individual co-treatment differences remain separately unverified.", "uncertainty": "The main comparator strategy was verified. Detailed dietary adherence and individual co-treatment differences remain separately unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The common dietary treatment, placebo composition and contemporaneous Table 3 comparison." }, { "item_id": "N07", "question_type": "Duration and phase linkage", "question": "Is the linkage between abstract and regulatory-table periods/phases verified?", "needed": "Original article visit schedules, titration/maintenance phases and an FDA trial-family crosswalk.", "role": "Required", "role_reason": "Needed to avoid automatically treating different duration labels as errors or replacing them with one value.", "application_exception": "The 16-week and 12-week definitions are not automatically conflicting data. Do not establish actual phase correspondence beyond the label.", "criterion": "Retain the label’s 16 weeks including 4-week titration and the abstract’s 12-week definition, with limits on exact phase linkage.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3: question-specific outcome adaptations are locally designed; M03 §3.2.1–3.2.4: dose, duration and effect-modification details are locally designed; M04 §4.6.3, M15 §15.3.1–15.3.3: state separation is locally designed — case-specific adaptation for duration and phase linkage.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare timelines and visit schedules side by side to verify phase linkage; do not arbitrarily adjust different durations.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "FDA Table 3 covers 16 weeks including 4-week titration; the publisher abstract describes 12 weeks of treatment. The original citation does not assert exact phase linkage beyond the label definition.", "condition_status": "Partly verified", "status_reason": "Both source definitions are explicit, but detailed phase linkage is unconfirmed.", "missingness": "Article visit durations and phase-specific participant/analysis correspondence in the label are unverified.", "uncertainty": "Article visit durations and phase-specific participant/analysis correspondence in the label are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original article visit schedules, titration/maintenance phases and an FDA trial-family crosswalk." }, { "item_id": "N08", "question_type": "Endpoint and unit", "question": "What are the selected outcome measure and unit?", "needed": "Table 3 mean percentage-change definition, units and baseline reference.", "role": "Required", "role_reason": "Needed to avoid mixing results measured differently or at other times, even for the same lipid.", "application_exception": "Do not replace mean LDL-C change with Table 5 medians/IQR, Table 4 at other times or TG.", "criterion": "Connect mean LDL-C percentage change from baseline at 16 weeks with the percentage-point contrast, distinguishing concentration, medians and other lipids.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3: question-specific outcome adaptations are locally designed; M08 Table 8.2.a, M03 §3.2.4: local application — case-specific adaptation for endpoint and unit.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Check table headings, footnotes and measures against original material; record differences between means/medians and concentration/%/percentage points.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The selected endpoint is mean LDL-C percentage change from baseline at 16 weeks in FDA Table 3. Arm values are percentages; the original arithmetic between-arm contrast is in percentage points.", "condition_status": "Met", "status_reason": "The endpoint, mean percentage change and units are explicit in the original calculation record and claim conditions.", "missingness": "This measure/unit was verified. Changes in mg/dL, other times or medians were not substituted as verified primary effects.", "uncertainty": "This measure/unit was verified. Changes in mg/dL, other times or medians were not substituted as verified primary effects.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Table 3 mean percentage-change definition, units and baseline reference." }, { "item_id": "N09", "question_type": "Design and allocation", "question": "Are the actual design, allocation and concealment implementation verified?", "needed": "Original methods for random sequence generation, allocation concealment and the baseline table.", "role": "Required", "role_reason": "Needed to avoid treating an RCT label alone as resolving allocation and confounding issues.", "application_exception": "Do not invent unreported parallel/crossover details or equate unverified allocation concealment with confirmed failure.", "criterion": "Show both the abstract’s randomized double-blind fixed-dose placebo-controlled description and unverified allocation implementation.", "basis": "M08 §8.1–8.2.3: local application — case-specific adaptation for design and allocation.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare sequence generation, enrolment/allocation procedures and concealment implementation with original methods, separating design labels from implementation verification.", "current_reports": [ "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The S16 abstract describes a randomized double-blind fixed-dose placebo-controlled design. Allocation-concealment implementation remains unverified without the article full text.", "condition_status": "Partly verified", "status_reason": "The design description is verified; implementation details remain unresolved.", "missingness": "Random sequence generation, allocation concealment and baseline-balance details are unverified.", "uncertainty": "Random sequence generation, allocation concealment and baseline-balance details are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original methods for random sequence generation, allocation concealment and the baseline table." }, { "item_id": "N10", "question_type": "Maintenance of blinding", "question": "Are maintenance of blinding and arm-specific assessment information verified?", "needed": "Participant, staff and assessor blinding procedures and assessments of maintained blinding.", "role": "Required", "role_reason": "A double-blind label does not replace an actual assessment of maintained blinding.", "application_exception": "Warnings about pharmacological-dose flushing alone do not establish unblinding.", "criterion": "Distinguish the double-blind description from actual maintenance/assessment procedures.", "basis": "M08 §8.1–8.2.3: local application; M08 Table 8.2.a, M03 §3.2.4: local application — case-specific adaptation for maintenance of blinding.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare who was blinded, blinding checks and assessor knowledge with original methods, considering limitations for objective lipid outcomes.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The abstract confirms a double-blind design, but checks of maintained blinding remain unverified without full text. Flushing warnings are not converted into evidence of actual blinding failure.", "condition_status": "Unverified", "status_reason": "The retained scope lacks the required actual blinding checks/assessment procedures.", "missingness": "Actual information about maintained blinding, assessor knowledge and arm-specific testing procedures is unverified.", "uncertainty": "Actual information about maintained blinding, assessor knowledge and arm-specific testing procedures is unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Participant, staff and assessor blinding procedures and assessments of maintained blinding." }, { "item_id": "N11", "question_type": "Co-treatment and diet", "question": "Are individual co-treatment and dietary exposures verified?", "needed": "Arm-specific total diet, concomitant drugs/vitamins, rescue treatment and change histories.", "role": "Required", "role_reason": "A common treatment background does not establish identical individual exposures.", "application_exception": "A description that this is not a B-complex intervention does not establish absence of concurrent vitamins in individuals.", "criterion": "Distinguish the common dietary background from actual differences in total diet and concurrent vitamins/treatment.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3: local application; M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed — case-specific adaptation for co-treatment and diet.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Extract co-treatment and dietary records by arm and review their handling in intervention strategies and selected analyses.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The dietary-treatment background and 2000 mg/day study drug are verified, but total diet and individual concurrent vitamin use are unconfirmed.", "condition_status": "Partly verified", "status_reason": "The common treatment scope was verified; actual individual exposures remain unresolved.", "missingness": "Total diet, co-treatment, rescue treatment, arm-specific changes and their handling are unverified.", "uncertainty": "Total diet, co-treatment, rescue treatment, arm-specific changes and their handling are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific total diet, concomitant drugs/vitamins, rescue treatment and change histories." }, { "item_id": "N12", "question_type": "Adherence and treatment deviations", "question": "Are actual adherence and the analytical handling of treatment deviations verified?", "needed": "Arm-specific adherence, stopping/dose changes and handling rules.", "role": "Required", "role_reason": "Needed to avoid filling missing actual exposure with 100% adherence or a PP analysis.", "application_exception": "Unverified adherence details do not establish that the intervention was never administered.", "criterion": "Connect prescribed doses to actual adherence, changes, stopping and their handling.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3: local application; M08 §8.2.2, M15 §15.3.1: local application — case-specific adaptation for adherence and treatment deviations.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link adherence/stopping tables to actual analysis populations and review differences between assignment-effect and adherence-effect interpretations.", "current_reports": [ "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original assessment verified trial dose and dietary comparator but left detailed actual adherence unconfirmed.", "condition_status": "Unverified", "status_reason": "Arm-specific adherence, treatment changes and analytical handling records were not acquired.", "missingness": "Actual adherence, stopping/changes and their effects on analysis are unverified.", "uncertainty": "Actual adherence, stopping/changes and their effects on analysis are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific adherence, stopping/dose changes and handling rules." }, { "item_id": "N13", "question_type": "Measurement procedures", "question": "Are the LDL-C assay and arm-specific measurement procedures verified?", "needed": "Original LDL-C assay, specimen/blood-sampling conditions and visit-specific measurement procedures.", "role": "Required", "role_reason": "Describing an objective marker does not verify every measurement procedure.", "application_exception": "Do not delete observed values because the assay is unverified or assert that laboratory interference actually occurred.", "criterion": "Distinguish objective blood-lipid measurement from the actual assay, sampling/visits and measurement limitations.", "basis": "M08 Table 8.2.a, M03 §3.2.4: local application; M03 §3.2.4, M15 §15.3.1–15.3.3: question-specific outcome adaptations are locally designed — case-specific adaptation for measurement procedures.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link the assay and sampling/visit schedules to result tables and review arm-specific differences in methods and timing.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original assessment describes objective blood-lipid markers. The retained summary read in this work does not verify detailed assays or specimen/sampling conditions.", "condition_status": "Partly verified", "status_reason": "The measurement target is verified; procedural details remain unresolved.", "missingness": "The LDL-C assay, sampling conditions, measurers and arm-specific visit procedures are unverified.", "uncertainty": "The LDL-C assay, sampling conditions, measurers and arm-specific visit procedures are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original LDL-C assay, specimen/blood-sampling conditions and visit-specific measurement procedures." }, { "item_id": "N14", "question_type": "Arm-specific observations", "question": "What are the LDL-C values for the two arms at the same time in Table 3?", "needed": "FDA Table 3 arm-specific values/footnotes and the article’s 2000 mg LDL result.", "role": "Required", "role_reason": "Favourable values must also retain their source attribution, without mixing values from other doses.", "application_exception": "Do not promote an observed decrease to adequate precision, prevention of clinical events or an individual success probability.", "criterion": "Retain mean percentage changes of −14% and −1% with their respective arms, table and time.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3: question-specific outcome adaptations are locally designed; M08 §8.2.2, M15 §15.3.1: local application — case-specific adaptation for arm-specific observations.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Re-extract the agreeing 2000 mg LDL values against the original table/abstract’s arm, endpoint and period definitions.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "Original Table 3 reports mean percentage changes of −14% in the 2000 mg arm and −1% with placebo. The article abstract agrees at −14% for 2000 mg LDL-C.", "condition_status": "Met", "status_reason": "The same arm-specific observations are retained in the current text and original calculation record.", "missingness": "These reported arm values and their attribution were verified. A new check of the physical original table, exact analysis n and CI was not performed.", "uncertainty": "These reported arm values and their attribution were verified. A new check of the physical original table, exact analysis n and CI was not performed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "FDA Table 3 arm-specific values/footnotes and the article’s 2000 mg LDL result." }, { "item_id": "N15", "question_type": "Historical contrast", "question": "What does the retained −13 percentage-point value represent?", "needed": "Original difference, unit, method and prohibited-conversion records.", "role": "Required", "role_reason": "Needed to retain the meaning of existing arithmetic without generating a new effect calculation.", "application_exception": "Do not rerun the calculation or reconstruct mg/dL changes without baseline concentrations, ARR, NNT, SMD or CI.", "criterion": "Record only the already-retained arithmetic contrast between arm-specific mean percentage changes; do not convert it to an adjusted effect, a new CI or concentration.", "basis": "M08 §8.2.2, M15 §15.3.1: local application; M15 §15.3.1–15.3.3: local application; M03 §3.2.4, M15 §15.3.1–15.3.3: question-specific outcome adaptations are locally designed — case-specific adaptation for the historical contrast.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Check the source, common time and direction of the retained arithmetic and whether wording transfers it to an adjusted estimate or clinical risk.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "−13 percentage points is the arithmetic contrast between −14% and −1% in the original ChatGPT calculation record. Its status is verification of the existing between-arm arithmetic contrast only; SE, SD, degrees of freedom and CI are null.", "condition_status": "Met", "status_reason": "The original arithmetic-only definition and prohibited conversions are directly connected.", "missingness": "Only the existing descriptive arithmetic contrast was verified. An adjusted causal mean difference, CI, SMD, ARR and NNT remain unverified; no new calculation was performed.", "uncertainty": "Only the existing descriptive arithmetic contrast was verified. An adjusted causal mean difference, CI, SMD, ARR and NNT remain unverified; no new calculation was performed.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original difference, unit, method and prohibited-conversion records." }, { "item_id": "N16", "question_type": "Effect of interest and analysis", "question": "Are the analysis population and model for the LDL-C contrast verified?", "needed": "Article analysis populations, estimands, models, adjustment and table-specific analysis methods.", "role": "Required", "role_reason": "Needed to avoid establishing ITT or an adjusted causal difference from an arithmetic contrast alone.", "application_exception": "Do not invent ITT/PP or adjusted values or use baseline n as actual analysis n.", "criterion": "Link ITT/PP, adjustment and completer/assignment effects to original analyses; do not invent unknown analyses.", "basis": "M08 §8.2.2, M15 §15.3.1: local application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4: design-specific adaptations are locally designed — case-specific adaptation for effect of interest and analysis.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link methods and participants to arm-specific result tables and compare with the effect of interest and missing-data/deviation handling.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original records verified only the arithmetic contrast; exact analysed, completed and dropout n and missing-data methods were unconfirmed. Conversion to an adjusted causal difference is also prohibited.", "condition_status": "Unverified", "status_reason": "The original article full text needed to verify exact analysis methods, populations and models is currently unavailable in the retained material.", "missingness": "ITT/PP, analysis populations, adjustment, estimands and models are unverified.", "uncertainty": "ITT/PP, analysis populations, adjustment, estimands and models are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Article analysis populations, estimands, models, adjustment and table-specific analysis methods." }, { "item_id": "N17", "question_type": "Allocation-to-analysis denominators", "question": "Are denominators from allocation through analysis verified for each arm?", "needed": "Arm-specific recruitment, allocation, completion, analysis and dropout flow, and Table 3 analysis n.", "role": "Required", "role_reason": "Needed to avoid automatically reusing the total 122 or baseline 41/40 as analysis denominators.", "application_exception": "The total 122 includes a 1000 mg arm. The 41/40 values are baseline n, not verified complete analysis n.", "criterion": "Distinguish and connect the total 122, key baseline 41/40 and actual analysed/completed/dropout denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4: design-specific adaptations are locally designed; M08 §8.2.2, M15 §15.3.1: local application — case-specific adaptation for allocation-to-analysis denominators.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Reconstruct each arm’s participant flow over time and verify correspondence between total/baseline samples and outcome-specific analysis denominators.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The trial total of 122 includes a 1000 mg arm; baseline n for the main contrast is 41 versus 40. The original sample-size role is baseline n, with completed/analysed sample sizes unverified.", "condition_status": "Partly verified", "status_reason": "Total and baseline denominators are verified; outcome-specific analysis flow remains unresolved.", "missingness": "Exact analysed, completed and dropout n for each arm and denominators at the Table 3 time point are unverified.", "uncertainty": "Exact analysed, completed and dropout n for each arm and denominators at the Table 3 time point are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific recruitment, allocation, completion, analysis and dropout flow, and Table 3 analysis n." }, { "item_id": "N18", "question_type": "Missing-data handling", "question": "Are the reasons for missing data/dropout and their handling verified?", "needed": "Arm-specific dropout reasons, missing LDL-C and imputation/sensitivity analyses.", "role": "Required", "role_reason": "Needed to avoid turning unknown dropout into 0 or an absence of bias.", "application_exception": "Do not turn unavailable information into a high dropout rate or a quantified, established bias.", "criterion": "Connect missing-data/dropout counts, reasons and handling to the selected analysis.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4: design-specific adaptations are locally designed; M08 §8.2.2, M15 §15.3.1: local application — case-specific adaptation for missing-data handling.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare missing-data tables with analysis methods and review whether results under alternative assumptions are available.", "current_reports": [ "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original assessment’s missing-data and unresolved-issue records state that exact analysed, completed and dropout n and missing-data methods remain unconfirmed because the full text was not accessed.", "condition_status": "Unverified", "status_reason": "The retained scope lacks the required loss/handling data.", "missingness": "Arm-specific dropout counts, reasons, missing-data handling and sensitivity results are unverified.", "uncertainty": "Arm-specific dropout counts, reasons, missing-data handling and sensitivity results are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific dropout reasons, missing LDL-C and imputation/sensitivity analyses." }, { "item_id": "N19", "question_type": "Dispersion and CI", "question": "Are dispersion and the between-arm CI reported for LDL-C percentage change at the same time?", "needed": "Arm-specific percentage-change dispersion, analysis n, between-arm CI and derivation methods.", "role": "Required", "role_reason": "Needed to avoid reconstructing precision from a significance threshold or an interval for another outcome.", "application_exception": "A statement that selected original regulatory tables do not report a value must not be extended to all articles.", "criterion": "Verify SD/SE for the relevant percentage changes and the between-arm CI at the same denominator and time.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4: design-specific adaptations are locally designed; M15 §15.3.1–15.3.3: local application — case-specific adaptation for dispersion and CI.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Directly verify dispersion/intervals for the relevant analysis and check for substitution of another table’s IQR or a cardiovascular HR CI.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "Standard error, change-score standard deviation, degrees of freedom, confidence level and interval are null. The retained record states that selected regulatory tables do not provide corresponding percentage-change dispersion or a lipid-contrast CI; Table 5 IQR and cardiovascular HR CIs were not substituted.", "condition_status": "Unverified", "status_reason": "Dispersion and CI for the same analysis were not acquired within the selected regulatory-table/abstract scope.", "missingness": "SD/SE, analysis n, CI and exact derivation methods for the selected lipid contrast are unverified.", "uncertainty": "SD/SE, analysis n, CI and exact derivation methods for the selected lipid contrast are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Arm-specific percentage-change dispersion, analysis n, between-arm CI and derivation methods." }, { "item_id": "N20", "question_type": "Testing and significance", "question": "Are the exact P value and test definition verified?", "needed": "Table 3 testing footnotes, exact P and multiplicity/adjustment methods.", "role": "Required", "role_reason": "Needed to avoid treating a significance threshold as adequate precision or effect size.", "application_exception": "P<0.05 is not an exact P, CI or SD. Do not invent nonsignificant or equivalence results.", "criterion": "Distinguish the table threshold P<0.05 from exact P, testing/adjustment and CI.", "basis": "M15 §15.3.1–15.3.3: local application; M08 §8.2.2, M15 §15.3.1: local application — case-specific adaptation for testing and significance.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Verify test definitions, analysis populations and comparisons subject to adjustment; do not calculate CI/dispersion from the threshold.", "current_reports": [ "S15" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original product information explicitly states that the table’s P<0.05 is not an exact P, CI or SD. Testing/adjustment details remain unverified in the current material.", "condition_status": "Partly verified", "status_reason": "The reported threshold is retained; exact testing/adjustment remains unresolved.", "missingness": "Exact P, test type, multiplicity/adjustment and analysis denominators are unverified.", "uncertainty": "Exact P, test type, multiplicity/adjustment and analysis denominators are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Table 3 testing footnotes, exact P and multiplicity/adjustment methods." }, { "item_id": "N21", "question_type": "Important difference", "question": "Can the between-arm interval be interpreted against a justified important difference?", "needed": "The LDL-C contrast CI, evidence for an important difference in this question and interpretation limits.", "role": "Required (precision interpretation)", "role_reason": "Needed to retain the observed lipid decrease without adding conclusions about sufficient effect or clinical benefit.", "application_exception": "Do not create common sample-size, duration or trial-count thresholds or use the original C/46/EX cap as a numerical important-difference criterion.", "criterion": "Link the reported CI to evidence for an important difference in this question; do not turn EX(a) into effect0 or failure to reach an MCID.", "basis": "M15 §15.3.1–15.3.3: local application; M03 §3.2.4: locally defined extension boundary — case-specific adaptation for important difference.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Review whether a justified important difference and the relevant interval are provided; otherwise, do not judge sufficiency from significance alone.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original imprecision assessment retains unconfirmed lipid between-arm CI/SD and EX(a), without converting them to E0 or failure to reach an MCID. Established clinical benefit is not overstated.", "condition_status": "Unverified", "status_reason": "The current material lacks a verified CI for this contrast and a justified important-difference criterion.", "missingness": "The effect range and its relationship to an important difference are unverified. The observed decrease itself was not converted to 0.", "uncertainty": "The effect range and its relationship to an important difference are unverified. The observed decrease itself was not converted to 0.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The LDL-C contrast CI, evidence for an important difference in this question and interpretation limits." }, { "item_id": "N22", "question_type": "Plans and registration", "question": "Do reported endpoints, times and analyses agree with the original plan?", "needed": "Initial registration, protocol, analysis plan and amendment history.", "role": "Required", "role_reason": "Needed to avoid establishing agreement with a registered 1st (primary) endpoint from the abstract/label alone.", "application_exception": "An NCT value of null does not establish nonregistration. An unavailable plan is not definitive evidence of selective reporting.", "criterion": "Verify only the portions actually compared between original registration/protocol/analysis plan and reported LDL-C results.", "basis": "M08 Table 8.2.a, M04 §4.6.3: local application; M04 §4.5, §4.6.3: current-record conversion limits derive from user scope and local design — case-specific adaptation for plans and registration.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare prespecified endpoints, times and analyses in original plans with result tables/articles to review changes and possible selective reporting.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The evidence list’s registration field is null; the text does not claim to have read initial registration or a protocol. The abstract alone did not verify agreement with a registered 1st (primary) endpoint.", "condition_status": "Unverified", "status_reason": "The required original plan is absent from the retained inputs.", "missingness": "Original plans, agreement of endpoints/analyses/times and reasons for amendments are unverified.", "uncertainty": "Original plans, agreement of endpoints/analyses/times and reasons for amendments are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Initial registration, protocol, analysis plan and amendment history." }, { "item_id": "N23", "question_type": "Reports and trial family", "question": "At what level are the article and label linked to the same trial family?", "needed": "Trial identifiers and population/arm/time crosswalks between the article and FDA trial tables.", "role": "Required", "role_reason": "Needed to avoid adding the article and FDA re-report as independent replications.", "application_exception": "The 2 bibliographic/regulatory reports are not 2 unique trials. Do not automatically merge other trial families in the full label into the same trial.", "criterion": "Link matching design/n/dose in the article and regulatory table without inventing a patient-level crosswalk or 2 independent trials.", "basis": "M04 §4.6.1–4.6.2: distinction between studies and reports; cohort/outcome linkage is local application; M04 §4.6.1–4.6.2, M15 §15.3.1: local application — case-specific adaptation for reports and trial family.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Review report–trial–outcome correspondence, distinguishing repeated citations of the same family from unconfirmed detailed links.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The S16 Morgan 1996 trial with 122 participants is strongly linked to S15 Table 3 by design/n/dose. The original citation limits this to less than a patient-level crosswalk. Original R1 records avoidance of double-counting the same trial arms.", "condition_status": "Partly verified", "status_reason": "There is strong linkage evidence for the same key contrast, but no detailed trial/participant crosswalk.", "missingness": "Exact family correspondence across all label trial groups, patient-level crosswalks and the overall unique-trial count are unverified.", "uncertainty": "Exact family correspondence across all label trial groups, patient-level crosswalks and the overall unique-trial count are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial identifiers and population/arm/time crosswalks between the article and FDA trial tables." }, { "item_id": "N24", "question_type": "Independent replication", "question": "Is independent replication of this question verified?", "needed": "Unique families, outcomes, funding and authorship for additional eligible trials.", "role": "Supplementary; required for replication claims", "role_reason": "Needed to avoid automatically promoting multiple label trials or original R1 into an independent-replication count.", "application_exception": "Unavailable additional eligible material does not mean 0 studies worldwide or no effect.", "criterion": "Link unique studies with the same product/population/measure to independent author and funding information.", "basis": "M04 §4.6.1–4.6.2, M15 §15.3.1: local application; M04 §4.6.1–4.6.2: distinction between studies and reports; cohort/outcome linkage is local application; Chamgap’s own independence/attribution condition. The official methodological sections used in this pilot do not guarantee all these details — case-specific adaptation for independent replication.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare eligible families, remove duplicate reports and record differences in conditions and unverified independence.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "Original R1 records avoiding double-counting the same trial arms. Multiple trials in the manufacturer table were not converted to R2 without verifying independent authors and funding.", "condition_status": "Unverified", "status_reason": "Independent author/funding records and unique result tables for the direct question were not acquired in the current inputs.", "missingness": "The number of independent direct replications and distribution of trial-specific conditions/results are unverified.", "uncertainty": "The number of independent direct replications and distribution of trial-specific conditions/results are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Unique families, outcomes, funding and authorship for additional eligible trials." }, { "item_id": "N25", "question_type": "Funding and COI", "question": "Are research funding, product provision and author interests verified?", "needed": "Complete original article funding, product provision, employment/patents and COI declarations.", "role": "Supplementary; required for independence claims", "role_reason": "Needed to avoid converting unavailable full text into certainty of manufacturer-only or independent research.", "application_exception": "Do not infer specific funding or the magnitude of bias from the NIASPAN product name or regulatory table alone.", "criterion": "Link actual full funding/COI declarations while retaining uncertainty about manufacturer-only or independent funding.", "basis": "Chamgap’s own independence/attribution condition. The official methodological sections used in this pilot do not guarantee all these details — case-specific adaptation for funding and COI.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare original declarations with authors/institutions and study families, recording verified interests separately from uncertainty.", "current_reports": [ "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The complete original article funding/COI statements were not accessed. Original I1 with uncertainty establishes neither manufacturer-only nor independent research.", "condition_status": "Unverified", "status_reason": "The full declaration text is absent from the current retained scope.", "missingness": "Actual research funding, product provision, employment/patents and declared COI are unverified.", "uncertainty": "Actual research funding, product provision, employment/patents and declared COI are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Complete original article funding, product provision, employment/patents and COI declarations." }, { "item_id": "N26", "question_type": "Inconsistent reports", "question": "Are the causes of inconsistent reports for other doses/endpoints verified?", "needed": "Relevant original publisher-abstract/regulatory-table data, phases/denominators and corrections for 1000 mg LDL, TG and related values.", "role": "Required", "role_reason": "Needed to avoid erasing related inconsistencies because some values agree or arbitrarily correcting them as rounding.", "application_exception": "A different dose alone is not automatically conflicting data. Retain only inconsistencies explicit in the current record; do not invent causes or new values.", "criterion": "Retain the agreeing 2000 mg LDL value and mark the causes of actual inconsistencies for other doses/endpoints as unverified.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3: state separation is locally designed; M04 §4.6.1–4.6.2, M15 §15.3.1: local application — case-specific adaptation for inconsistent reports.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare dose, measure, time and denominator for each inconsistent item, distinguishing conflicting reports of the same contrast from values under different conditions.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The retained record states that some publisher-abstract and regulatory-table values disagree, including 1000 mg LDL percentage change. Only the agreeing 2000 mg LDL −14% and each duration definition were adopted; inconsistencies of unknown cause were not asserted to be rounding.", "condition_status": "Conflicting data", "status_reason": "The original inconsistency review explicitly records disagreement and unconfirmed causes.", "missingness": "The relevant original inconsistent values, phase/denominator crosswalks and causes/corrections are currently unverified. The agreeing 2000 mg LDL value itself was not marked as conflicting.", "uncertainty": "The relevant original inconsistent values, phase/denominator crosswalks and causes/corrections are currently unverified. The agreeing 2000 mg LDL value itself was not marked as conflicting.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Relevant original publisher-abstract/regulatory-table data, phases/denominators and corrections for 1000 mg LDL, TG and related values." }, { "item_id": "N27", "question_type": "Extension to clinical events", "question": "Does LDL-C change answer whether myocardial infarction or mortality is prevented?", "needed": "Direct event studies with the same strategy/population if extending to events or mortality.", "role": "Supplementary; required for clinical-event extensions", "role_reason": "Needed to avoid automatically converting surrogate improvement into prevention of clinical events.", "application_exception": "Do not require an event trial for the narrow LDL-C percentage-change question. This table does not assess event prevention.", "criterion": "Separate the lipid-change question from event/mortality questions.", "basis": "M03 §3.2.4: locally defined extension boundary — case-specific adaptation for extension to clinical events.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "If an extension is claimed, review event-study populations, formulations, comparators and durations in a separate eligibility table.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original key interpretation and reader answer distinguish lipid decreases from patient clinical benefit and do not interpret them as reduced myocardial infarction or mortality.", "condition_status": "Not applicable", "status_reason": "The current main question concerns marker change and has not been extended to event prevention.", "missingness": "An event-trial requirement is inapplicable to this narrow question. Direct event prevention with the same strategy/population was not verified in this work.", "uncertainty": "An event-trial requirement is inapplicable to this narrow question. Direct event prevention with the same strategy/population was not verified in this work.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Direct event studies with the same strategy/population if extending to events or mortality." }, { "item_id": "N28", "question_type": "Dose and long-term extensions", "question": "Does the result answer questions about optimal dose, long-term maintenance or specific subgroups?", "needed": "Direct dose comparisons, long-term follow-up and prespecified subgroup/interaction data if extending the claim.", "role": "Supplementary; required for the relevant extension", "role_reason": "Needed to avoid transferring one key dose/period to optimization or maintenance effects.", "application_exception": "The presence of a 1000 mg arm does not establish an optimal dose. Do not require every long-term/subgroup study for the narrow 16-week question.", "criterion": "Do not extend the fixed-comparison 16-week result to optimal dose, long-term persistence or effect modification.", "basis": "M03 §3.2.1–3.2.4: dose, duration and effect-modification details are locally designed — case-specific adaptation for dose and long-term extensions.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Review direct comparisons, follow-up and interactions separately for extensions outside the original question; do not average supporting arms of the same trial.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The current scope is 2000 mg/day versus diet plus placebo over 16 weeks including titration. The 1000 mg arm is a supporting record; do not create a pooled mean, optimal dose or long-term effect.", "condition_status": "Not applicable", "status_reason": "Optimal dose, long-term persistence and subgroups are extensions of the selected question and are not claimed in this table.", "missingness": "The extension requirement is inapplicable. Direct effects on optimal dose, long-term maintenance and subgroups were not newly verified.", "uncertainty": "The extension requirement is inapplicable. Direct effects on optimal dose, long-term maintenance and subgroups were not newly verified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Direct dose comparisons, long-term follow-up and prespecified subgroup/interaction data if extending the claim." }, { "item_id": "N29", "question_type": "Harm collection and denominators", "question": "Are arm-specific harm collection, event/person counts and stopping denominators verified for the key trial?", "needed": "The key trial’s AE definitions, collection, people/events, stopping, exposure time and arm-specific denominators.", "role": "Supplementary; required for harm/safety claims", "role_reason": "The presence of efficacy data or regulatory warnings does not establish complete harm counts in the same trial.", "application_exception": "Do not use FDA2020 pooled safety data as event rates in this trial or convert unverified harms into harmlessness or AE0.", "criterion": "Separate original warnings from actual arm-specific harm counts in the key small trial; do not use pooled data as trial event rates.", "basis": "M19 §19.1.2–19.2.4: local application; M19 §19.1.2–19.2.4: detailed distinctions are locally designed; M19 §19.1.2–19.2.4, M04 §4.6.3: local application — case-specific adaptation for harm collection and denominators.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link arm-specific safety tables/collection procedures to follow-up and check which trials contribute to FDA pooled data.", "current_reports": [ "S15" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "Warnings about flushing and elevated liver enzymes, glucose and urate at prescription doses are retained. Arm-specific AE denominators in the key small trial are unconfirmed; FDA2020 pooled data were not used as this trial’s event rates.", "condition_status": "Partly verified", "status_reason": "The official document’s warning scope is linked; systematic collection/counts in the selected trial remain unresolved.", "missingness": "AE people/events, stopping, arm-specific denominators/time and complete collection scope in the selected trial are unverified.", "uncertainty": "AE people/events, stopping, arm-specific denominators/time and complete collection scope in the selected trial are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "The key trial’s AE definitions, collection, people/events, stopping, exposure time and arm-specific denominators." }, { "item_id": "N30", "question_type": "Harm timing and alternatives", "question": "Are temporal order, co-treatment and alternative comparative causes verified for harms in the selected trial?", "needed": "Trial AE onset, stopping/recovery, concurrent medication/baseline disease, comparisons and long-term vulnerable-group data.", "role": "Supplementary; required for harm causality/scope", "role_reason": "Needed to avoid automatically extending label warnings to causal risk estimates or overall safety in the selected trial.", "application_exception": "Do not invent rechallenge, recovery, incidence or rare long-term-risk values from a summary without event counts. No H07 independent replicated-harm claim is made in this work.", "criterion": "Link warnings to actual timing, comparisons and alternatives in the same population/exposure, without converting a signal to a causal rate.", "basis": "M19 §19.1.2–19.2.4: local application; M19 §19.2: design-specific harm questions, with locally designed temporal details; M19 §19.2.2–19.2.4, M03 §3.2.3: local application; M19 §19.2.2–19.2.4: design considerations, with locally designed confounding records; Chamgap’s own interpretive boundary. M19 principles inform this work; no official causality tool was executed — case-specific adaptation for harm timing and alternatives.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Link exposure/event timelines and co-treatment to actual counts and review the possible scope of causal, frequency and long-term extrapolation.", "current_reports": [ "S15" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original safety detail retains warnings about pharmacological-dose nicotinic acid but leaves selected-trial arm-specific harm denominators unconfirmed. Actual temporal order, co-treatment/alternatives and stopping/recovery outcomes are not verified in these inputs.", "condition_status": "Unverified", "status_reason": "The current warning summary does not provide selected-trial timing, comparative or alternative-cause data.", "missingness": "Temporal order, co-treatment/alternatives, comparisons/causality and long-term vulnerable-group scope for selected-trial harms are unverified.", "uncertainty": "Temporal order, co-treatment/alternatives, comparisons/causality and long-term vulnerable-group scope for selected-trial harms are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Trial AE onset, stopping/recovery, concurrent medication/baseline disease, comparisons and long-term vulnerable-group data." }, { "item_id": "N31", "question_type": "Laboratory interference", "question": "Within what scope was reported laboratory interference verified?", "needed": "FDA7.6 assay-specific interference conditions and the original trial LDL-C assay/interference observations.", "role": "Supplementary; required for interference claims", "role_reason": "Needed to avoid extending label interference warnings to invalidation of this trial’s LDL-C effect or interference with all tests.", "application_exception": "Do not add test names, mechanisms or frequencies absent from the original inputs or assert that LDL-C interference occurred.", "criterion": "Do not convert original assay-specific warnings into actual LDL-C measurement errors or effects on all tests.", "basis": "M19 §19.1.2–19.2.4: local application; M19 §19.1.2–19.2.4: detailed distinctions are locally designed; Chamgap’s own interpretive boundary. M19 principles inform this work; no official causality tool was executed; M08 Table 8.2.a, M03 §3.2.4: local application — case-specific adaptation for laboratory interference.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare assay-specific conditions in the official document with original measurement methods, separating general warnings from interference observed in the trial.", "current_reports": [ "S15" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The current text includes specific laboratory-interference warnings and the original citation links FDA Section 7.6, printed page 9. This summary lacks assay-specific details and evidence of actual LDL-C interference in the selected trial.", "condition_status": "Partly verified", "status_reason": "Warnings and historical locations are verified; assay-specific details and actual trial interference remain unresolved.", "missingness": "Assay-specific interference conditions and actual interference in selected-trial LDL-C testing are unverified.", "uncertainty": "Assay-specific interference conditions and actual interference in selected-trial LDL-C testing are unverified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "FDA7.6 assay-specific interference conditions and the original trial LDL-C assay/interference observations." }, { "item_id": "N32", "question_type": "Material reading", "question": "Which material was actually read in this work?", "needed": "Current input SHA, material type/URL, historical access locations, individual access dates and global review date.", "role": "Required", "role_reason": "Needed to avoid converting reading of the retained summary into current reading of FDA PDFs, articles or DOI-linked full texts.", "application_exception": "Citations have no individual access dates. Do not infer that the 2026-09-14 review date was an actual access date or automatically inherit report access for the DOI entry.", "criterion": "Distinguish original-byte retained summaries, historical access in original citations and current external access not attempted/unread for each material.", "basis": "M04 §4.5–4.6: material-collection/selection principles; access/reading separation and the hyperlink contract are locally designed; M04 §4.5, §4.6.3: current-record conversion limits derive from user scope and local design — case-specific adaptation for material reading.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare existence, acquisition, reading status and original locations by report, separating blue summary links from unread external full texts.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The complete original-byte retained summary was read in this work. Historical access was S15 regulatory PDF text/selected table screenshots and S16 abstract/bibliography. External PDFs and publisher/DOI pages were not attempted, acquired or read in this work; individual access dates remain null.", "condition_status": "Met", "status_reason": "Current actual reading and original recorded access levels were separately connected by material.", "missingness": "The current retained-summary reading scope was verified. Current access to external originals, physical/identifier agreement, full text and licensing were not verified.", "uncertainty": "The current retained-summary reading scope was verified. Current access to external originals, physical/identifier agreement, full text and licensing were not verified.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Current input SHA, material type/URL, historical access locations, individual access dates and global review date." }, { "item_id": "N33", "question_type": "Verification scope and history", "question": "What search, correction and history scope is retained?", "needed": "Existing search records, 5 corrections, inputs used and the unpublished/registration verification scope.", "role": "Required", "role_reason": "Needed to avoid promoting old internal validation/web indexing to a current exhaustive clinical search.", "application_exception": "Separate original verification reports, source lists and shared correction records were not opened in this work; S17/S19 without citations are not made into new reports.", "criterion": "Distinguish the 2026-09-14 web indexing/existing searches/corrections from this local conversion.", "basis": "M04 §4.5, §4.6.3: current-record conversion limits derive from user scope and local design; M04 §4.6.3, M15 §15.3.1–15.3.3: state separation is locally designed; M08 Table 8.2.a, M04 §4.6.3: local application — case-specific adaptation for verification scope and history.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Check the scope actually retained for search logs/corrections and limit uncertainty statements to the relevant sections/dates.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "The original search is described as 2026-09-14 web indexing, a supplied index of 3081 entries/related originals and direct publisher/FDA/NHLBI sources. It was not a complete systematic PubMed search or exhaustive search of unpublished material; original wording/references for 5 corrections remain unchanged.", "condition_status": "Met", "status_reason": "The reported scope of earlier searches/corrections and the boundary of work not performed now were verified.", "missingness": "Separate old search/verification/shared-correction originals and current unpublished/registration, correction or retraction checks were not reviewed in this work.", "uncertainty": "Separate old search/verification/shared-correction originals and current unpublished/registration, correction or retraction checks were not reviewed in this work.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Existing search records, 5 corrections, inputs used and the unpublished/registration verification scope." }, { "item_id": "N34", "question_type": "Original assessment and table status", "question": "How are original assessments/numbers distinguished from table-review status?", "needed": "Original grade/score/axes, calculation records, gaps, corrections and original internal-review metadata.", "role": "Required (display boundary)", "role_reason": "Needed to avoid interpreting blue verification in the table as a new clinical-efficacy grade, fulfilment percentage or official certification.", "application_exception": "Original document-quality A and internal validation are distinct from evidence C/46. Table preparation, another author’s QA, technical/UI checks and publication are also separate statuses.", "criterion": "Retain C46, original axes/EX/CX, original caution, nulls and historical arithmetic; table-preparation verification is not efficacy/safety certification.", "basis": "M03 §3.1, §3.2.1–3.2.4: question-clarification principles; detailed separation rules are locally designed; M04 §4.5, §4.6.3: current-record conversion limits derive from user scope and local design; M15 §15.3.1–15.3.3: local application; Chamgap’s own interpretive boundary. M19 principles inform this work; no official causality tool was executed — case-specific adaptation for original assessment and table status.", "condition_origin": "Locally developed conditions fitted to a known retained case; not blinded or preregistered validation or official clinical certification.", "proposed_research": "Compare the complete retained summary with derived tables, separating technical checks from content review of unchanged original values/nulls, inconsistencies and condition states.", "current_reports": [ "S15", "S16" ], "existence": "Records verified in retained bibliographic and linked summaries, distinct from checking current external originals.", "acquired_read": "Retained summary read · external originals unread", "observation": "Original grade C/score 46, B/S/R1/I1/EX/B1/CX, caution and all nulls/corrections/historical arithmetic remain unchanged. Condition states indicate item-specific verification within current retained material, not a new clinical assessment or success probability.", "condition_status": "Met", "status_reason": "Original current values and limits of table conversion/condition states were separately recorded.", "missingness": "Original-value preservation and the production-review scope were verified. Independent clinical certification, official methodological assessment and current external full-text verification were not performed. The earlier unpublished-website record describes its historical state, distinct from current publication status.", "uncertainty": "Original-value preservation and the production-review scope were verified. Independent clinical certification, official methodological assessment and current external full-text verification were not performed. The earlier unpublished-website record describes its historical state, distinct from current publication status.", "review_date": "2026-10-05", "reading_status": "Original unread · retained summary read", "additional_material": "Original grade/score/axes, calculation records, gaps, corrections and original internal-review metadata." } ], "reports": [ { "report_id": "S15", "title": "NIASPAN (niacin extended-release tablets), FDA prescribing information revised 09/2020", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf", "report_type": "Regulatory re-report of the key LDL trial; other trials/pooled safety in the full label have separate scopes", "existence": "Retained bibliographic details, URLs and result attribution were verified. Current external responses, physical originals and licensing were not verified.", "acquired_read": "Retained Korean/English summaries and case-specific condition/application records were read. External PDFs, abstracts, full texts and registration were not attempted, acquired or read in this work.", "study_family": "NIASPAN-Morgan-122-supported", "independent_replication": false, "observed_result": "Retain Table 3 mean LDL-C percentage change of −14% with 2000 mg, contemporaneous placebo −1% and the existing −13 percentage-point contrast. The 16 weeks include 4-week titration. Baseline 41/40 are not analysis n; dispersion/CI and trial-specific AE denominators are unverified. Do not fill gaps with other tables, medians or pooled safety.", "result_level": "Historical review summaries and source locations are retained. This is not renewed verification of external originals or a new clinical assessment.", "source_evidence_date": "2026-09-14", "materials": [ { "material_type": "FDA prescribing-information full PDF", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Regulatory re-report of the key LDL trial; other trials/pooled safety in the full label have separate scopes; external originals were not attempted, acquired or read. Only the retained URL is provided; access, acquisition and reading were not attempted in this work. Individual historical access dates are unrecorded and distinct from the original evidence review date." }, { "material_type": "Retained bibliographic, evidence and manuscript summary", "public_status": "Internally retained summary", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Retained existing review summary read", "as_of": "2026-10-05", "qualification": "The retained summary was acquired and read. This is not an original-byte copy of a clinical full text." } ], "links": [ { "label": "Official source", "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf" } ] }, { "report_id": "S16", "title": "Morgan et al. Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients with Hypercholesterolemia: A Placebo-controlled Trial", "url": "https://journals.sagepub.com/doi/10.1177/107424849600100302", "report_type": "Article abstract/bibliography for the same key trial; patient-level crosswalk unverified", "existence": "Retained bibliographic details, URLs and result attribution were verified. Current external responses, physical originals and licensing were not verified.", "acquired_read": "Retained Korean/English summaries and case-specific condition/application records were read. External PDFs, abstracts, full texts and registration were not attempted, acquired or read in this work.", "study_family": "NIASPAN-Morgan-122-supported", "independent_replication": false, "observed_result": "A randomized double-blind fixed-dose placebo-controlled trial with 122 participants in total. The abstract’s −14% LDL result at 2000 mg agrees with the regulatory table; retain the abstract’s 12-week definition and the label’s 16 weeks including titration. Full funding/COI, exact analysis/missing-data handling and causes of inconsistencies for other doses/endpoints are unverified.", "result_level": "Historical review summaries and source locations are retained. This is not renewed verification of external originals or a new clinical assessment.", "source_evidence_date": "2026-09-14", "materials": [ { "material_type": "Publisher article abstract/bibliography webpage", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "Article abstract/bibliography for the same key trial; patient-level crosswalk unverified; external originals were not attempted, acquired or read. Only the retained URL is provided; access, acquisition and reading were not attempted in this work. Individual historical access dates are unrecorded and distinct from the original evidence review date." }, { "material_type": "Retained bibliographic, evidence and manuscript summary", "public_status": "Internally retained summary", "access_status": "Retained copy acquired; summary read", "acquired": true, "actually_read": "Retained existing review summary read", "as_of": "2026-10-05", "qualification": "The retained summary was acquired and read. This is not an original-byte copy of a clinical full text." }, { "material_type": "DOI bibliographic entry", "public_status": "Current public availability unverified", "access_status": "External access not attempted; not acquired", "acquired": false, "actually_read": "Unread", "as_of": "2026-10-05", "qualification": "An article-identifier entry, not evidence of full-text acquisition or actual reading. Only the retained URL is provided; access, acquisition and reading were not attempted in this work. Individual historical access dates are unrecorded and distinct from the original evidence review date. The DOI entry does not automatically inherit historical abstract/bibliography access." } ], "links": [ { "label": "Official source", "url": "https://journals.sagepub.com/doi/10.1177/107424849600100302" } ] } ], "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; distinguish intervention variants.", "review_level": "Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed." }, { "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 studies solely because outcomes are unreported.", "review_level": "Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed." }, { "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, then review randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed." }, { "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 effects, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed." }, { "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 different from efficacy questions. Case reports do not establish incidence.", "review_level": "Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed." } ], "status_dictionary": { "Met": "Identity, attribution and scope for this condition are verified in retained material, separately from clinical sufficiency/certification.", "Partly verified": "Some information is verified; actual methods, denominators or procedures remain unresolved.", "Unverified": "Required clinical data/values are unverified within this reading scope. This does not mean effect0, harmlessness or unfinished table preparation.", "Conflicting data": "Inconsistent reports in original records, distinct from differences in dose/time alone.", "Not applicable": "An extension requirement outside the narrow lipid question is inapplicable; not a substitute for unread material.", "Not applicable (spaced alias)": "Grey alias for Not applicable.", "Unread": "External originals were not directly read in this work, distinct from reading retained summaries.", "Review incomplete": "A label for unfinished item-specific table review. This case’s retained-record review is complete, separately from unverified clinical data and unread external originals." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "S15 and S16 are strongly linked by matching design, sample size and dose to the key NIASPAN-Morgan-122-supported trial. A patient-level crosswalk is unverified. The 2 reports are not counted as 2 independent trials/replications; other trials and pooled safety in the full label have separate scopes. Overall unique-study, participant and independent direct-replication counts are unverified." }, "history": [ { "date": "2026-10-29", "kind": "Public reader/material separation", "view_version": "1.0", "change": "Prepared a public reader and materials from the existing 34 items. No new clinical search, verification-state change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-29" }