# Nicotinic acid (prescription NIASPAN extended-release tablets) × Mean LDL-C percentage change in primary hypercholesterolaemia Verdict 3083 · Evidence Check Stored-material review date: 2026-10-05 Original evidence review date: 2026-09-14 Review-criteria version: 1.0 Public page/material preparation date: 2026-10-29 Clinical papers were not read directly; existing review summaries were checked. No new clinical-literature search was performed. Unverified does not mean that research is absent or that there is no effect. ## Assessment scope - Population: Primary hypercholesterolaemia with LDL-C >160 mg/dL despite dietary management. This is distinct from deficiency correction and an add-on statin strategy. - Ingredient, formulation and route: 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. - Measured outcome: 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. - Questions outside this scope: Deficiency correction, add-on statin TG strategies and other vitamin B3 formulations; Extensions to myocardial infarction, mortality, optimal dose, long-term effects or subgroups ## Checklist items ### N01 · Which NIASPAN LDL-C contrast is retained? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The exact assessed claim, claim conditions and editorial scope support this single question. - Reason for missing information: 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. - Required materials and conditions: Exact locations for the assessed claim, claim conditions and editorial scope, and the canonical URL. - Materials to obtain first: Exact locations for the assessed claim, claim conditions and editorial scope, and the canonical URL. - Further research: First fix the question and report-eligibility table, then check whether other formulations, TG or clinical-event questions have entered the scope. - Conditions for verification: Connect the exact assessed claim, formulation, population, diet plus placebo, 2000 mg/day and 16 weeks including titration as one question. - Why this condition is needed: Needed to keep this LDL-C marker question separate from the full original multi-lipid assessment. - Application exceptions: The subclaim array is empty. Do not automatically generate tables for other doses/endpoints or rewrite 128/2346. - Remaining 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. - Referenced methods: 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. - Related sources: S15, S16 ### N02 · Are eligibility criteria and baseline characteristics verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The diagnosis and LDL entry criterion are stated; detailed recruitment and baseline composition remain unresolved. - Reason for missing information: Detailed age, comorbidities, eligibility and baseline balance between arms are unverified. - Required materials and conditions: The original article’s inclusion/exclusion criteria, age, baseline table and preceding dietary procedures. - Materials to obtain first: The original article’s inclusion/exclusion criteria, age, baseline table and preceding dietary procedures. - Further research: Check recruitment criteria and baseline tables against the target and included populations, including selection limitations. - Conditions for verification: Connect primary hypercholesterolaemia with LDL-C >160 mg/dL despite dietary management to actual eligibility and baseline characteristics. - Why this condition is needed: Needed to avoid transferring results in a high-LDL population to all adults, CKD or add-on statin strategies. - Application exceptions: Distinguish the planned adult-population question from unverified age/comorbidity details; do not establish a failure of representativeness. - Remaining uncertainty: Detailed age, comorbidities, eligibility and baseline balance between arms are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N03 · Does this trial concern correction of B3 deficiency? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: The retained record states that the trial did not select nutritional deficiency and that the abstract/tables used contained no diagnostic B3 concentration data. - Why unverified: The non-deficiency selection boundary and the limited concentration-reporting scope were verified. - Reason for missing information: The scope was verified as a trial not selected for deficiency. Individual B3 deficiency status and baseline concentrations were not verified. - Required materials and conditions: Deficiency-based selection, baseline B3 concentrations and eligibility definitions. - Materials to obtain first: Deficiency-based selection, baseline B3 concentrations and eligibility definitions. - Further research: Check whether original recruitment criteria required deficiency; do not pool deficiency-correction evidence as a high-LDL treatment effect. - Conditions for verification: Distinguish a trial not selected for deficiency from the limited scope of unreported B3 concentrations in the abstract/tables. - Why this condition is needed: Needed to distinguish nutritional-deficiency treatment from lipid changes at pharmacological doses. - Application exceptions: Unreported B3 concentrations do not establish laboratory-confirmed absence of deficiency. Do not require concentration measurement unconditionally for the narrow lipid question. - Remaining uncertainty: The scope was verified as a trial not selected for deficiency. Individual B3 deficiency status and baseline concentrations were not verified. - Referenced methods: 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. - Related sources: S15, S16 ### N04 · What are the selected ingredient, formulation and route? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: The original records identify oral NIASPAN nicotinic acid extended-release and record that other niacin forms are not equivalent. - Why unverified: Retained ingredient, formulation and route identities agree. - Reason for missing information: This product/route boundary was verified. Current physical labelling, product approval and manufacturing origin were not newly verified. - Required materials and conditions: Original labelling and product identity for NIASPAN ingredient, ER formulation and oral route. - Materials to obtain first: Original labelling and product identity for NIASPAN ingredient, ER formulation and oral route. - Further 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. - Conditions for verification: Distinguish oral NIASPAN nicotinic acid extended-release tablets from other B3 forms. - Why this condition is needed: Needed to avoid assigning the same effects/harms to other molecules or release formulations. - Application exceptions: Do not combine general vitamin B3, inositol hexanicotinate, nicotinamide or other formulations as direct evidence. - Remaining uncertainty: This product/route boundary was verified. Current physical labelling, product approval and manufacturing origin were not newly verified. - Referenced methods: M03 §3.2.2–3.2.3: reverse labelling and laboratory adaptations are locally designed — case-specific adaptation for ingredient and formulation. - Related sources: S15, S16 ### N05 · Are the target dose, titration and actual administration history verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The target dose and titration-inclusive definition were verified; detailed actual exposure is unavailable. - Reason for missing information: Doses at each titration visit, adherence and actual cumulative exposure are unverified. - Required materials and conditions: Arm-specific titration schedules, administration/stopping histories and actual doses. - Materials to obtain first: Arm-specific titration schedules, administration/stopping histories and actual doses. - Further research: Reconstruct exposure during titration and maintenance, then compare actual doses and deviations with intended prescribing. - Conditions for verification: Distinguish the target 2000 mg/day, 4-week titration and actual administration/adherence. - Why this condition is needed: Needed to avoid treating the target 2000 mg as actual exposure throughout the entire period. - Application exceptions: The 1000 mg arm in the same trial is a supporting record; do not create a pooled mean dose. - Remaining uncertainty: Doses at each titration visit, adherence and actual cumulative exposure are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N06 · What is the main comparator strategy? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The comparator conditions and the current article/regulatory-table comparison scope are explicit. - Reason for missing information: The main comparator strategy was verified. Detailed dietary adherence and individual co-treatment differences remain separately unverified. - Required materials and conditions: The common dietary treatment, placebo composition and contemporaneous Table 3 comparison. - Materials to obtain first: The common dietary treatment, placebo composition and contemporaneous Table 3 comparison. - Further research: Compare intervention/control strategies and exclude add-on statin TG strategies and other times in the dose-escalation table. - Conditions for verification: Connect contemporaneous 2000 mg and placebo arms on the same dietary background. - Why this condition is needed: The comparison must retain the same time/background to preserve attribution of the LDL-C difference. - Application exceptions: Do not substitute AIM-HIGH’s low-dose IR control or statin ± ezetimibe strategy for this placebo. - Remaining uncertainty: The main comparator strategy was verified. Detailed dietary adherence and individual co-treatment differences remain separately unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N07 · Is the linkage between abstract and regulatory-table periods/phases verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Both source definitions are explicit, but detailed phase linkage is unconfirmed. - Reason for missing information: Article visit durations and phase-specific participant/analysis correspondence in the label are unverified. - Required materials and conditions: Original article visit schedules, titration/maintenance phases and an FDA trial-family crosswalk. - Materials to obtain first: Original article visit schedules, titration/maintenance phases and an FDA trial-family crosswalk. - Further research: Compare timelines and visit schedules side by side to verify phase linkage; do not arbitrarily adjust different durations. - Conditions for verification: Retain the label’s 16 weeks including 4-week titration and the abstract’s 12-week definition, with limits on exact phase linkage. - Why this condition is needed: Needed to avoid automatically treating different duration labels as errors or replacing them with one value. - Application exceptions: The 16-week and 12-week definitions are not automatically conflicting data. Do not establish actual phase correspondence beyond the label. - Remaining uncertainty: Article visit durations and phase-specific participant/analysis correspondence in the label are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N08 · What are the selected outcome measure and unit? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The endpoint, mean percentage change and units are explicit in the original calculation record and claim conditions. - Reason for missing information: This measure/unit was verified. Changes in mg/dL, other times or medians were not substituted as verified primary effects. - Required materials and conditions: Table 3 mean percentage-change definition, units and baseline reference. - Materials to obtain first: Table 3 mean percentage-change definition, units and baseline reference. - Further research: Check table headings, footnotes and measures against original material; record differences between means/medians and concentration/%/percentage points. - Conditions for verification: Connect mean LDL-C percentage change from baseline at 16 weeks with the percentage-point contrast, distinguishing concentration, medians and other lipids. - Why this condition is needed: Needed to avoid mixing results measured differently or at other times, even for the same lipid. - Application exceptions: Do not replace mean LDL-C change with Table 5 medians/IQR, Table 4 at other times or TG. - Remaining uncertainty: This measure/unit was verified. Changes in mg/dL, other times or medians were not substituted as verified primary effects. - Referenced methods: 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. - Related sources: S15, S16 ### N09 · Are the actual design, allocation and concealment implementation verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: The S16 abstract describes a randomized double-blind fixed-dose placebo-controlled design. Allocation-concealment implementation remains unverified without the article full text. - Why unverified: The design description is verified; implementation details remain unresolved. - Reason for missing information: Random sequence generation, allocation concealment and baseline-balance details are unverified. - Required materials and conditions: Original methods for random sequence generation, allocation concealment and the baseline table. - Materials to obtain first: Original methods for random sequence generation, allocation concealment and the baseline table. - Further research: Compare sequence generation, enrolment/allocation procedures and concealment implementation with original methods, separating design labels from implementation verification. - Conditions for verification: Show both the abstract’s randomized double-blind fixed-dose placebo-controlled description and unverified allocation implementation. - Why this condition is needed: Needed to avoid treating an RCT label alone as resolving allocation and confounding issues. - Application exceptions: Do not invent unreported parallel/crossover details or equate unverified allocation concealment with confirmed failure. - Remaining uncertainty: Random sequence generation, allocation concealment and baseline-balance details are unverified. - Referenced methods: M08 §8.1–8.2.3: local application — case-specific adaptation for design and allocation. - Related sources: S16 ### N10 · Are maintenance of blinding and arm-specific assessment information verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The retained scope lacks the required actual blinding checks/assessment procedures. - Reason for missing information: Actual information about maintained blinding, assessor knowledge and arm-specific testing procedures is unverified. - Required materials and conditions: Participant, staff and assessor blinding procedures and assessments of maintained blinding. - Materials to obtain first: Participant, staff and assessor blinding procedures and assessments of maintained blinding. - Further research: Compare who was blinded, blinding checks and assessor knowledge with original methods, considering limitations for objective lipid outcomes. - Conditions for verification: Distinguish the double-blind description from actual maintenance/assessment procedures. - Why this condition is needed: A double-blind label does not replace an actual assessment of maintained blinding. - Application exceptions: Warnings about pharmacological-dose flushing alone do not establish unblinding. - Remaining uncertainty: Actual information about maintained blinding, assessor knowledge and arm-specific testing procedures is unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N11 · Are individual co-treatment and dietary exposures verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: The dietary-treatment background and 2000 mg/day study drug are verified, but total diet and individual concurrent vitamin use are unconfirmed. - Why unverified: The common treatment scope was verified; actual individual exposures remain unresolved. - Reason for missing information: Total diet, co-treatment, rescue treatment, arm-specific changes and their handling are unverified. - Required materials and conditions: Arm-specific total diet, concomitant drugs/vitamins, rescue treatment and change histories. - Materials to obtain first: Arm-specific total diet, concomitant drugs/vitamins, rescue treatment and change histories. - Further research: Extract co-treatment and dietary records by arm and review their handling in intervention strategies and selected analyses. - Conditions for verification: Distinguish the common dietary background from actual differences in total diet and concurrent vitamins/treatment. - Why this condition is needed: A common treatment background does not establish identical individual exposures. - Application exceptions: A description that this is not a B-complex intervention does not establish absence of concurrent vitamins in individuals. - Remaining uncertainty: Total diet, co-treatment, rescue treatment, arm-specific changes and their handling are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N12 · Are actual adherence and the analytical handling of treatment deviations verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: The original assessment verified trial dose and dietary comparator but left detailed actual adherence unconfirmed. - Why unverified: Arm-specific adherence, treatment changes and analytical handling records were not acquired. - Reason for missing information: Actual adherence, stopping/changes and their effects on analysis are unverified. - Required materials and conditions: Arm-specific adherence, stopping/dose changes and handling rules. - Materials to obtain first: Arm-specific adherence, stopping/dose changes and handling rules. - Further research: Link adherence/stopping tables to actual analysis populations and review differences between assignment-effect and adherence-effect interpretations. - Conditions for verification: Connect prescribed doses to actual adherence, changes, stopping and their handling. - Why this condition is needed: Needed to avoid filling missing actual exposure with 100% adherence or a PP analysis. - Application exceptions: Unverified adherence details do not establish that the intervention was never administered. - Remaining uncertainty: Actual adherence, stopping/changes and their effects on analysis are unverified. - Referenced methods: 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. - Related sources: S16 ### N13 · Are the LDL-C assay and arm-specific measurement procedures verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: The original assessment describes objective blood-lipid markers. The retained summary read in this work does not verify detailed assays or specimen/sampling conditions. - Why unverified: The measurement target is verified; procedural details remain unresolved. - Reason for missing information: The LDL-C assay, sampling conditions, measurers and arm-specific visit procedures are unverified. - Required materials and conditions: Original LDL-C assay, specimen/blood-sampling conditions and visit-specific measurement procedures. - Materials to obtain first: Original LDL-C assay, specimen/blood-sampling conditions and visit-specific measurement procedures. - Further research: Link the assay and sampling/visit schedules to result tables and review arm-specific differences in methods and timing. - Conditions for verification: Distinguish objective blood-lipid measurement from the actual assay, sampling/visits and measurement limitations. - Why this condition is needed: Describing an objective marker does not verify every measurement procedure. - Application exceptions: Do not delete observed values because the assay is unverified or assert that laboratory interference actually occurred. - Remaining uncertainty: The LDL-C assay, sampling conditions, measurers and arm-specific visit procedures are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N14 · What are the LDL-C values for the two arms at the same time in Table 3? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The same arm-specific observations are retained in the current text and original calculation record. - Reason for missing information: 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. - Required materials and conditions: FDA Table 3 arm-specific values/footnotes and the article’s 2000 mg LDL result. - Materials to obtain first: FDA Table 3 arm-specific values/footnotes and the article’s 2000 mg LDL result. - Further research: Re-extract the agreeing 2000 mg LDL values against the original table/abstract’s arm, endpoint and period definitions. - Conditions for verification: Retain mean percentage changes of −14% and −1% with their respective arms, table and time. - Why this condition is needed: Favourable values must also retain their source attribution, without mixing values from other doses. - Application exceptions: Do not promote an observed decrease to adequate precision, prevention of clinical events or an individual success probability. - Remaining 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. - Referenced methods: 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. - Related sources: S15, S16 ### N15 · What does the retained −13 percentage-point value represent? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: −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. - Why unverified: The original arithmetic-only definition and prohibited conversions are directly connected. - Reason for missing information: 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. - Required materials and conditions: Original difference, unit, method and prohibited-conversion records. - Materials to obtain first: Original difference, unit, method and prohibited-conversion records. - Further research: Check the source, common time and direction of the retained arithmetic and whether wording transfers it to an adjusted estimate or clinical risk. - Conditions for verification: 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. - Why this condition is needed: Needed to retain the meaning of existing arithmetic without generating a new effect calculation. - Application exceptions: Do not rerun the calculation or reconstruct mg/dL changes without baseline concentrations, ARR, NNT, SMD or CI. - Remaining 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. - Referenced methods: 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. - Related sources: S15, S16 ### N16 · Are the analysis population and model for the LDL-C contrast verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The original article full text needed to verify exact analysis methods, populations and models is currently unavailable in the retained material. - Reason for missing information: ITT/PP, analysis populations, adjustment, estimands and models are unverified. - Required materials and conditions: Article analysis populations, estimands, models, adjustment and table-specific analysis methods. - Materials to obtain first: Article analysis populations, estimands, models, adjustment and table-specific analysis methods. - Further research: Link methods and participants to arm-specific result tables and compare with the effect of interest and missing-data/deviation handling. - Conditions for verification: Link ITT/PP, adjustment and completer/assignment effects to original analyses; do not invent unknown analyses. - Why this condition is needed: Needed to avoid establishing ITT or an adjusted causal difference from an arithmetic contrast alone. - Application exceptions: Do not invent ITT/PP or adjusted values or use baseline n as actual analysis n. - Remaining uncertainty: ITT/PP, analysis populations, adjustment, estimands and models are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N17 · Are denominators from allocation through analysis verified for each arm? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Total and baseline denominators are verified; outcome-specific analysis flow remains unresolved. - Reason for missing information: Exact analysed, completed and dropout n for each arm and denominators at the Table 3 time point are unverified. - Required materials and conditions: Arm-specific recruitment, allocation, completion, analysis and dropout flow, and Table 3 analysis n. - Materials to obtain first: Arm-specific recruitment, allocation, completion, analysis and dropout flow, and Table 3 analysis n. - Further research: Reconstruct each arm’s participant flow over time and verify correspondence between total/baseline samples and outcome-specific analysis denominators. - Conditions for verification: Distinguish and connect the total 122, key baseline 41/40 and actual analysed/completed/dropout denominators. - Why this condition is needed: Needed to avoid automatically reusing the total 122 or baseline 41/40 as analysis denominators. - Application exceptions: The total 122 includes a 1000 mg arm. The 41/40 values are baseline n, not verified complete analysis n. - Remaining uncertainty: Exact analysed, completed and dropout n for each arm and denominators at the Table 3 time point are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N18 · Are the reasons for missing data/dropout and their handling verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The retained scope lacks the required loss/handling data. - Reason for missing information: Arm-specific dropout counts, reasons, missing-data handling and sensitivity results are unverified. - Required materials and conditions: Arm-specific dropout reasons, missing LDL-C and imputation/sensitivity analyses. - Materials to obtain first: Arm-specific dropout reasons, missing LDL-C and imputation/sensitivity analyses. - Further research: Compare missing-data tables with analysis methods and review whether results under alternative assumptions are available. - Conditions for verification: Connect missing-data/dropout counts, reasons and handling to the selected analysis. - Why this condition is needed: Needed to avoid turning unknown dropout into 0 or an absence of bias. - Application exceptions: Do not turn unavailable information into a high dropout rate or a quantified, established bias. - Remaining uncertainty: Arm-specific dropout counts, reasons, missing-data handling and sensitivity results are unverified. - Referenced methods: 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. - Related sources: S16 ### N19 · Are dispersion and the between-arm CI reported for LDL-C percentage change at the same time? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Dispersion and CI for the same analysis were not acquired within the selected regulatory-table/abstract scope. - Reason for missing information: SD/SE, analysis n, CI and exact derivation methods for the selected lipid contrast are unverified. - Required materials and conditions: Arm-specific percentage-change dispersion, analysis n, between-arm CI and derivation methods. - Materials to obtain first: Arm-specific percentage-change dispersion, analysis n, between-arm CI and derivation methods. - Further research: Directly verify dispersion/intervals for the relevant analysis and check for substitution of another table’s IQR or a cardiovascular HR CI. - Conditions for verification: Verify SD/SE for the relevant percentage changes and the between-arm CI at the same denominator and time. - Why this condition is needed: Needed to avoid reconstructing precision from a significance threshold or an interval for another outcome. - Application exceptions: A statement that selected original regulatory tables do not report a value must not be extended to all articles. - Remaining uncertainty: SD/SE, analysis n, CI and exact derivation methods for the selected lipid contrast are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N20 · Are the exact P value and test definition verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The reported threshold is retained; exact testing/adjustment remains unresolved. - Reason for missing information: Exact P, test type, multiplicity/adjustment and analysis denominators are unverified. - Required materials and conditions: Table 3 testing footnotes, exact P and multiplicity/adjustment methods. - Materials to obtain first: Table 3 testing footnotes, exact P and multiplicity/adjustment methods. - Further research: Verify test definitions, analysis populations and comparisons subject to adjustment; do not calculate CI/dispersion from the threshold. - Conditions for verification: Distinguish the table threshold P<0.05 from exact P, testing/adjustment and CI. - Why this condition is needed: Needed to avoid treating a significance threshold as adequate precision or effect size. - Application exceptions: P<0.05 is not an exact P, CI or SD. Do not invent nonsignificant or equivalence results. - Remaining uncertainty: Exact P, test type, multiplicity/adjustment and analysis denominators are unverified. - Referenced methods: 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. - Related sources: S15 ### N21 · Can the between-arm interval be interpreted against a justified important difference? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The current material lacks a verified CI for this contrast and a justified important-difference criterion. - Reason for missing information: The effect range and its relationship to an important difference are unverified. The observed decrease itself was not converted to 0. - Required materials and conditions: The LDL-C contrast CI, evidence for an important difference in this question and interpretation limits. - Materials to obtain first: The LDL-C contrast CI, evidence for an important difference in this question and interpretation limits. - Further research: Review whether a justified important difference and the relevant interval are provided; otherwise, do not judge sufficiency from significance alone. - Conditions for verification: 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. - Why this condition is needed: Needed to retain the observed lipid decrease without adding conclusions about sufficient effect or clinical benefit. - Application exceptions: 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. - Remaining uncertainty: The effect range and its relationship to an important difference are unverified. The observed decrease itself was not converted to 0. - Referenced methods: M15 §15.3.1–15.3.3: local application; M03 §3.2.4: locally defined extension boundary — case-specific adaptation for important difference. - Related sources: S15, S16 ### N22 · Do reported endpoints, times and analyses agree with the original plan? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The required original plan is absent from the retained inputs. - Reason for missing information: Original plans, agreement of endpoints/analyses/times and reasons for amendments are unverified. - Required materials and conditions: Initial registration, protocol, analysis plan and amendment history. - Materials to obtain first: Initial registration, protocol, analysis plan and amendment history. - Further research: Compare prespecified endpoints, times and analyses in original plans with result tables/articles to review changes and possible selective reporting. - Conditions for verification: Verify only the portions actually compared between original registration/protocol/analysis plan and reported LDL-C results. - Why this condition is needed: Needed to avoid establishing agreement with a registered 1st (primary) endpoint from the abstract/label alone. - Application exceptions: An NCT value of null does not establish nonregistration. An unavailable plan is not definitive evidence of selective reporting. - Remaining uncertainty: Original plans, agreement of endpoints/analyses/times and reasons for amendments are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N23 · At what level are the article and label linked to the same trial family? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: There is strong linkage evidence for the same key contrast, but no detailed trial/participant crosswalk. - Reason for missing information: Exact family correspondence across all label trial groups, patient-level crosswalks and the overall unique-trial count are unverified. - Required materials and conditions: Trial identifiers and population/arm/time crosswalks between the article and FDA trial tables. - Materials to obtain first: Trial identifiers and population/arm/time crosswalks between the article and FDA trial tables. - Further research: Review report–trial–outcome correspondence, distinguishing repeated citations of the same family from unconfirmed detailed links. - Conditions for verification: Link matching design/n/dose in the article and regulatory table without inventing a patient-level crosswalk or 2 independent trials. - Why this condition is needed: Needed to avoid adding the article and FDA re-report as independent replications. - Application exceptions: 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. - Remaining uncertainty: Exact family correspondence across all label trial groups, patient-level crosswalks and the overall unique-trial count are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N24 · Is independent replication of this question verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Independent author/funding records and unique result tables for the direct question were not acquired in the current inputs. - Reason for missing information: The number of independent direct replications and distribution of trial-specific conditions/results are unverified. - Required materials and conditions: Unique families, outcomes, funding and authorship for additional eligible trials. - Materials to obtain first: Unique families, outcomes, funding and authorship for additional eligible trials. - Further research: Compare eligible families, remove duplicate reports and record differences in conditions and unverified independence. - Conditions for verification: Link unique studies with the same product/population/measure to independent author and funding information. - Why this condition is needed: Needed to avoid automatically promoting multiple label trials or original R1 into an independent-replication count. - Application exceptions: Unavailable additional eligible material does not mean 0 studies worldwide or no effect. - Remaining uncertainty: The number of independent direct replications and distribution of trial-specific conditions/results are unverified. - Referenced methods: 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. - Related sources: S15, S16 ### N25 · Are research funding, product provision and author interests verified? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: The complete original article funding/COI statements were not accessed. Original I1 with uncertainty establishes neither manufacturer-only nor independent research. - Why unverified: The full declaration text is absent from the current retained scope. - Reason for missing information: Actual research funding, product provision, employment/patents and declared COI are unverified. - Required materials and conditions: Complete original article funding, product provision, employment/patents and COI declarations. - Materials to obtain first: Complete original article funding, product provision, employment/patents and COI declarations. - Further research: Compare original declarations with authors/institutions and study families, recording verified interests separately from uncertainty. - Conditions for verification: Link actual full funding/COI declarations while retaining uncertainty about manufacturer-only or independent funding. - Why this condition is needed: Needed to avoid converting unavailable full text into certainty of manufacturer-only or independent research. - Application exceptions: Do not infer specific funding or the magnitude of bias from the NIASPAN product name or regulatory table alone. - Remaining uncertainty: Actual research funding, product provision, employment/patents and declared COI are unverified. - Referenced methods: 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. - Related sources: S16 ### N26 · Are the causes of inconsistent reports for other doses/endpoints verified? Verification status: Conflicting data Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The original inconsistency review explicitly records disagreement and unconfirmed causes. - Reason for missing information: 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. - Required materials and conditions: Relevant original publisher-abstract/regulatory-table data, phases/denominators and corrections for 1000 mg LDL, TG and related values. - Materials to obtain first: Relevant original publisher-abstract/regulatory-table data, phases/denominators and corrections for 1000 mg LDL, TG and related values. - Further research: Compare dose, measure, time and denominator for each inconsistent item, distinguishing conflicting reports of the same contrast from values under different conditions. - Conditions for verification: Retain the agreeing 2000 mg LDL value and mark the causes of actual inconsistencies for other doses/endpoints as unverified. - Why this condition is needed: Needed to avoid erasing related inconsistencies because some values agree or arbitrarily correcting them as rounding. - Application exceptions: A different dose alone is not automatically conflicting data. Retain only inconsistencies explicit in the current record; do not invent causes or new values. - Remaining 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. - Referenced methods: 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. - Related sources: S15, S16 ### N27 · Does LDL-C change answer whether myocardial infarction or mortality is prevented? Verification status: Not applicable Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The current main question concerns marker change and has not been extended to event prevention. - Reason for missing information: An event-trial requirement is inapplicable to this narrow question. Direct event prevention with the same strategy/population was not verified in this work. - Required materials and conditions: Direct event studies with the same strategy/population if extending to events or mortality. - Materials to obtain first: Direct event studies with the same strategy/population if extending to events or mortality. - Further research: If an extension is claimed, review event-study populations, formulations, comparators and durations in a separate eligibility table. - Conditions for verification: Separate the lipid-change question from event/mortality questions. - Why this condition is needed: Needed to avoid automatically converting surrogate improvement into prevention of clinical events. - Application exceptions: Do not require an event trial for the narrow LDL-C percentage-change question. This table does not assess event prevention. - Remaining 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. - Referenced methods: M03 §3.2.4: locally defined extension boundary — case-specific adaptation for extension to clinical events. - Related sources: S15, S16 ### N28 · Does the result answer questions about optimal dose, long-term maintenance or specific subgroups? Verification status: Not applicable Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Optimal dose, long-term persistence and subgroups are extensions of the selected question and are not claimed in this table. - Reason for missing information: The extension requirement is inapplicable. Direct effects on optimal dose, long-term maintenance and subgroups were not newly verified. - Required materials and conditions: Direct dose comparisons, long-term follow-up and prespecified subgroup/interaction data if extending the claim. - Materials to obtain first: Direct dose comparisons, long-term follow-up and prespecified subgroup/interaction data if extending the claim. - Further research: Review direct comparisons, follow-up and interactions separately for extensions outside the original question; do not average supporting arms of the same trial. - Conditions for verification: Do not extend the fixed-comparison 16-week result to optimal dose, long-term persistence or effect modification. - Why this condition is needed: Needed to avoid transferring one key dose/period to optimization or maintenance effects. - Application exceptions: 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. - Remaining uncertainty: The extension requirement is inapplicable. Direct effects on optimal dose, long-term maintenance and subgroups were not newly verified. - Referenced methods: 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. - Related sources: S15, S16 ### N29 · Are arm-specific harm collection, event/person counts and stopping denominators verified for the key trial? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The official document’s warning scope is linked; systematic collection/counts in the selected trial remain unresolved. - Reason for missing information: AE people/events, stopping, arm-specific denominators/time and complete collection scope in the selected trial are unverified. - Required materials and conditions: The key trial’s AE definitions, collection, people/events, stopping, exposure time and arm-specific denominators. - Materials to obtain first: The key trial’s AE definitions, collection, people/events, stopping, exposure time and arm-specific denominators. - Further research: Link arm-specific safety tables/collection procedures to follow-up and check which trials contribute to FDA pooled data. - Conditions for verification: Separate original warnings from actual arm-specific harm counts in the key small trial; do not use pooled data as trial event rates. - Why this condition is needed: The presence of efficacy data or regulatory warnings does not establish complete harm counts in the same trial. - Application exceptions: Do not use FDA2020 pooled safety data as event rates in this trial or convert unverified harms into harmlessness or AE0. - Remaining uncertainty: AE people/events, stopping, arm-specific denominators/time and complete collection scope in the selected trial are unverified. - Referenced methods: 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. - Related sources: S15 ### N30 · Are temporal order, co-treatment and alternative comparative causes verified for harms in the selected trial? Verification status: Unverified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The current warning summary does not provide selected-trial timing, comparative or alternative-cause data. - Reason for missing information: Temporal order, co-treatment/alternatives, comparisons/causality and long-term vulnerable-group scope for selected-trial harms are unverified. - Required materials and conditions: Trial AE onset, stopping/recovery, concurrent medication/baseline disease, comparisons and long-term vulnerable-group data. - Materials to obtain first: Trial AE onset, stopping/recovery, concurrent medication/baseline disease, comparisons and long-term vulnerable-group data. - Further research: Link exposure/event timelines and co-treatment to actual counts and review the possible scope of causal, frequency and long-term extrapolation. - Conditions for verification: Link warnings to actual timing, comparisons and alternatives in the same population/exposure, without converting a signal to a causal rate. - Why this condition is needed: Needed to avoid automatically extending label warnings to causal risk estimates or overall safety in the selected trial. - Application exceptions: 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. - Remaining uncertainty: Temporal order, co-treatment/alternatives, comparisons/causality and long-term vulnerable-group scope for selected-trial harms are unverified. - Referenced methods: 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. - Related sources: S15 ### N31 · Within what scope was reported laboratory interference verified? Verification status: Partly verified Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Warnings and historical locations are verified; assay-specific details and actual trial interference remain unresolved. - Reason for missing information: Assay-specific interference conditions and actual interference in selected-trial LDL-C testing are unverified. - Required materials and conditions: FDA7.6 assay-specific interference conditions and the original trial LDL-C assay/interference observations. - Materials to obtain first: FDA7.6 assay-specific interference conditions and the original trial LDL-C assay/interference observations. - Further research: Compare assay-specific conditions in the official document with original measurement methods, separating general warnings from interference observed in the trial. - Conditions for verification: Do not convert original assay-specific warnings into actual LDL-C measurement errors or effects on all tests. - Why this condition is needed: Needed to avoid extending label interference warnings to invalidation of this trial’s LDL-C effect or interference with all tests. - Application exceptions: Do not add test names, mechanisms or frequencies absent from the original inputs or assert that LDL-C interference occurred. - Remaining uncertainty: Assay-specific interference conditions and actual interference in selected-trial LDL-C testing are unverified. - Referenced methods: 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. - Related sources: S15 ### N32 · Which material was actually read in this work? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Current actual reading and original recorded access levels were separately connected by material. - Reason for missing information: The current retained-summary reading scope was verified. Current access to external originals, physical/identifier agreement, full text and licensing were not verified. - Required materials and conditions: Current input SHA, material type/URL, historical access locations, individual access dates and global review date. - Materials to obtain first: Current input SHA, material type/URL, historical access locations, individual access dates and global review date. - Further research: Compare existence, acquisition, reading status and original locations by report, separating blue summary links from unread external full texts. - Conditions for verification: Distinguish original-byte retained summaries, historical access in original citations and current external access not attempted/unread for each material. - Why this condition is needed: Needed to avoid converting reading of the retained summary into current reading of FDA PDFs, articles or DOI-linked full texts. - Application exceptions: 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. - Remaining uncertainty: The current retained-summary reading scope was verified. Current access to external originals, physical/identifier agreement, full text and licensing were not verified. - Referenced methods: 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. - Related sources: S15, S16 ### N33 · What search, correction and history scope is retained? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: The reported scope of earlier searches/corrections and the boundary of work not performed now were verified. - Reason for missing information: Separate old search/verification/shared-correction originals and current unpublished/registration, correction or retraction checks were not reviewed in this work. - Required materials and conditions: Existing search records, 5 corrections, inputs used and the unpublished/registration verification scope. - Materials to obtain first: Existing search records, 5 corrections, inputs used and the unpublished/registration verification scope. - Further research: Check the scope actually retained for search logs/corrections and limit uncertainty statements to the relevant sections/dates. - Conditions for verification: Distinguish the 2026-09-14 web indexing/existing searches/corrections from this local conversion. - Why this condition is needed: Needed to avoid promoting old internal validation/web indexing to a current exhaustive clinical search. - Application exceptions: 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. - Remaining uncertainty: Separate old search/verification/shared-correction originals and current unpublished/registration, correction or retraction checks were not reviewed in this work. - Referenced methods: 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. - Related sources: S15, S16 ### N34 · How are original assessments/numbers distinguished from table-review status? Verification status: Met Reading scope: Retained summary read · external originals unread - Current findings: 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. - Why unverified: Original current values and limits of table conversion/condition states were separately recorded. - Reason for missing information: 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. - Required materials and conditions: Original grade/score/axes, calculation records, gaps, corrections and original internal-review metadata. - Materials to obtain first: Original grade/score/axes, calculation records, gaps, corrections and original internal-review metadata. - Further research: Compare the complete retained summary with derived tables, separating technical checks from content review of unchanged original values/nulls, inconsistencies and condition states. - Conditions for verification: Retain C46, original axes/EX/CX, original caution, nulls and historical arithmetic; table-preparation verification is not efficacy/safety certification. - Why this condition is needed: Needed to avoid interpreting blue verification in the table as a new clinical-efficacy grade, fulfilment percentage or official certification. - Application exceptions: 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. - Remaining 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. - Referenced methods: 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. - Related sources: S15, S16 ## Evidence and sources ### S15 NIASPAN (niacin extended-release tablets), FDA prescribing information revised 09/2020 [Official source](https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf) Materials actually 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. Findings recorded in the summary: 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. Record level: Historical review summaries and source locations are retained. This is not renewed verification of external originals or a new clinical assessment. Independent replication: 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | FDA prescribing-information full PDF | Current public availability unverified | External access not attempted; not acquired | Unread | 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. | | Retained bibliographic, evidence and manuscript summary | Internally retained summary | Retained copy acquired; summary read | Retained existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. | ### S16 Morgan et al. Treatment Effect of Niaspan, a Controlled-release Niacin, in Patients with Hypercholesterolemia: A Placebo-controlled Trial [Official source](https://journals.sagepub.com/doi/10.1177/107424849600100302) Materials actually 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. Findings recorded in the summary: 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. Record level: Historical review summaries and source locations are retained. This is not renewed verification of external originals or a new clinical assessment. Independent replication: 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. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Publisher article abstract/bibliography webpage | Current public availability unverified | External access not attempted; not acquired | Unread | 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. | | Retained bibliographic, evidence and manuscript summary | Internally retained summary | Retained copy acquired; summary read | Retained existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. | | DOI bibliographic entry | Current public availability unverified | External access not attempted; not acquired | Unread | 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. | ## Review criteria and methods These are Chamgap's own application conditions, informed by the relevant sections of official methodological guidance. They do not constitute official assessment-tool certification or a new efficacy score. - M03 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03) · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13 · Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants. · Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed. - M04 [Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04) · §4.5, §4.6.1–4.6.3, MECIR C42 · Distinguish and link studies and reports; do not omit studies solely because outcomes are unreported. · Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed. - M08 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08) · §8.1–8.2.3, Table 8.2.a · Fix the outcome and effect of interest, then review randomization, deviations, missing data, measurement and selective reporting. · Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed. - M15 [Cochrane Handbook 6.5 (2024), chapter updated 2023-08](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15) · §15.2.4, §15.3.1–15.3.3 · Distinguish effects, intervals, importance and applicability. Sample size alone does not determine precision. · Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed. - M19 [Cochrane Handbook 6.5 (2024), chapter updated 2019-10](https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19) · §19.1.2, §19.2.1–19.2.4 · Harm questions may require designs, populations and follow-up different from efficacy questions. Case reports do not establish incidence. · Retained methodological-application records were reused. External originals were not reread and methodological content was not reassessed. ## What the statuses mean - 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. ## Change history 2026-10-29 · Public page/materials 1.0. Prepared a public reader and materials from the existing 34 items. No new clinical search, verification-state change or scoring was performed.