# Nicotinic acid (prescription NIASPAN ER tablets added to LDL-targeted statin therapy) × Two-year triglyceride percentage change Verdict 3082 · 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: 2026-10-28 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: Adults ≥45 with established ASCVD and low-HDL/residual dyslipidaemia tolerating niacin run-in. Entry TG >150 and <400 mg/dL off statins or >100 and <400 on statins. Not a nutrient-deficiency treatment cohort. - Ingredient, formulation and route: Nicotinic acid (prescription NIASPAN ER tablets added to LDL-targeted statin therapy) - Dose: 1500–2000 mg/day; control includes IR niacin 100–150 mg/day - Comparator: Both groups used simvastatin 40–80 mg/day±ezetimibe 10 mg/day for LDL-C 40–80 mg/dL. Control contained IR niacin 50 mg/tablet (100–150 mg/day). Actual background doses were titrated, so this is a treatment-strategy contrast, not identical fixed background dosing. - Measured outcome: Reported TG percentage change from baseline at 2 years: page endpoint. Trial 1st (primary): cardiovascular composite; lipids were a protocol 3rd (tertiary) objective. - Duration: 2-year lipid assessment; trial stopped early after approximately 3 years; 4–8-week run-in before randomization - Questions outside this scope: At 2 years in AIM-HIGH, reported triglyceride changes were −28.6% with the ER-niacin strategy and −8.1% with control, an arithmetic contrast of −20.5 percentage points. This is not cardiovascular-event prevention or evidence for every formulation and dose in all hypertriglyceridaemia. [S15; S17]; 3414 participants and 1718/1696 are randomized counts; the 2-year TG analysis denominator is unverified. The historical arithmetic contrast −20.5 percentage points is not a formal adjusted mean difference, mg/dL difference, ARR or NNT. The mean/median estimator, TG CI, SD and missing-data handling also remain unverified.; This pharmacological regimen has flushing, liver-enzyme, glucose/urate and specific laboratory-interference risks. Study-drug discontinuation of 25.4% versus 20.1% is not loss to follow-up. The 4–8-week tolerability run-in limits safety generalization to all starters. Safety details are from the fixed 2020 FDA source, not new current prescribing guidance. Research doses are not personal dosing instructions. [S15:safety; S15:interference; S17:discontinuation; S18:runin]; Retain original C, 46, Caution, B/S/R1/I1/EX/B1/CX and the historical grade-revalidation record. No new scoring was performed. Do not extend to generic B3, other formulations, deficiency correction, all high-TG populations, optimal dose, persistence beyond 2 years or personal prescribing. ## Checklist items ### N01 · Is the independent claim specifically the 2-year TG percentage change? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original claim is “2-year triglyceride percentage change”. It concerns TG changes with NIASPAN ER added to LDL-targeted treatment versus a low-dose IR-niacin control strategy. The subclaim list is empty. - Why unverified: The original manuscript and claim conditions identify the TG question. Clinical events, LDL and other formulations are outside it. - Reason for missing information: No gap in the identity of this narrow question. - Required materials and conditions: The original claim linked to the AIM-HIGH question elements. - Materials to obtain first: The original claim linked to the AIM-HIGH question elements. - Further research: Compare manuscript and trial identities; separate independent claims when question elements differ. - Conditions for verification: Link the original effect claim, actual intervention, population, comparator and time to the TG question. - Why this condition is needed: Needed to keep a surrogate decrease separate from clinical-event prevention and other lipid results. - Application exceptions: Korean/English are languages of the same question; an empty subclaim list does not create new claims. - Remaining uncertainty: No gap in the identity of this narrow question. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N02 · Is the chemical form, formulation and route actually oral NIASPAN ER tablets? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retained material specifies oral nicotinic-acid NIASPAN extended-release tablets. It excludes nicotinamide and inositol hexanicotinate; the intervention is not a B-complex product. - Why unverified: Chemical form, formulation and oral route are specified. This does not establish the same effect for generic B3 products. - Reason for missing information: Manufacturing origin is addressed separately in N09. - Required materials and conditions: Product formulation, ingredient and route records. - Materials to obtain first: Product formulation, ingredient and route records. - Further research: Match product name, chemical form and formulation across drug documents and trial records; analyze other products separately. - Conditions for verification: Link nicotinic acid, NIASPAN ER tablets and the oral route to the retained source identity. - Why this condition is needed: Needed to avoid treating generic vitamin B3 or other derivatives as the same intervention. - Application exceptions: Nicotinamide, inositol hexanicotinate and no-flush products are different interventions. - Remaining uncertainty: Manufacturing origin is addressed separately in N09. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N03 · Is the target dose of the selected add-on strategy verified? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The NIASPAN ER target was 1500–2000 mg/day. This is the add-on strategy range in selected tolerators, not a verified individual actual dose or optimal dose. - Why unverified: The target dose is specified in the claim conditions and original scope. Individually achieved dosing is not thereby verified. - Reason for missing information: Individual dosing/adherence histories and optimal dose remain unverified. - Required materials and conditions: Target titration plan and individual actual dosing/adherence records. - Materials to obtain first: Target titration plan and individual actual dosing/adherence records. - Further research: Trace arm-specific doses, titration and dosing histories to distinguish target from actual dose. - Conditions for verification: Verify the selected NIASPAN ER target dose and limit extensions to actual achieved or optimal dose. - Why this condition is needed: Needed to distinguish target dosing from individually achieved dosing and optimal dose. - Application exceptions: The 1500–2000 mg/day target range is not a single fixed dose or the achieved dose of every participant. - Remaining uncertainty: Individual dosing/adherence histories and optimal dose remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S19 ### N04 · Does the control strategy contain low-dose IR niacin? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The control contained IR niacin 50 mg/tablet, totaling 100–150 mg/day. This is not NIASPAN monotherapy versus no treatment. - Why unverified: Control composition and dose identify the actual comparison. Do not relabel it a wholly inactive placebo. - Reason for missing information: No current gap in this control identity. - Required materials and conditions: Control-tablet composition, dose and masking plan. - Materials to obtain first: Control-tablet composition, dose and masking plan. - Further research: Compare control composition, tablet count and dose with the original plan and intervention records. - Conditions for verification: Include IR niacin 50 mg/tablet and 100–150 mg/day in the selected comparison. - Why this condition is needed: Needed to avoid misreading a low-dose active masking ingredient as no treatment or a wholly inactive placebo. - Application exceptions: The presence of low-dose IR does not establish equivalent dosing/formulation to ER or a monotherapy comparison. - Remaining uncertainty: No current gap in this control identity. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S19 ### N05 · Was background treatment titrated to the same LDL target in both groups? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Both groups titrated simvastatin 40–80 mg/day±ezetimibe 10 mg/day to LDL-C 40–80 mg/dL. Actual background dosing was not fixed identically, so this is a strategy comparison. - Why unverified: The manuscript clearly describes target-treatment strategies. It does not establish identical individual fixed background doses. - Reason for missing information: Individual and arm-specific actual-dose distributions remain unverified in the retained material. - Required materials and conditions: Background-drug targets, arm-specific titration and actual doses. - Materials to obtain first: Background-drug targets, arm-specific titration and actual doses. - Further research: Compare target treatment, co-treatment changes and adherence by arm; define the effect as a strategy contrast. - Conditions for verification: Verify simvastatin/ezetimibe ranges and the LDL target; distinguish identical fixed-dose treatment. - Why this condition is needed: Needed to avoid attributing statin/ezetimibe titration differences solely to fixed-dose NIASPAN. - Application exceptions: A common target does not imply identical actual arm doses or require every treatment change to match. - Remaining uncertainty: Individual and arm-specific actual-dose distributions remain unverified in the retained material. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S19 ### N06 · Are the selected ASCVD/low-HDL population and entry TG criteria verified? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Participants were adults age 45 and older with established ASCVD and low-HDL/residual dyslipidaemia. Entry TG was >150 and <400 mg/dL off statins, or >100 and <400 mg/dL on statins. - Why unverified: The sources distinguish population and entry TG ranges. Do not generalize to all adults with high TG. - Reason for missing information: Additional details of the full baseline-characteristics table remain unverified. - Required materials and conditions: Eligibility/exclusion criteria and actual recruited-population characteristics. - Materials to obtain first: Eligibility/exclusion criteria and actual recruited-population characteristics. - Further research: Compare eligibility with baseline characteristics and assess directness for other high-TG populations. - Conditions for verification: Verify age 45 and older, established ASCVD/low HDL and statin-dependent entry TG ranges. - Why this condition is needed: Needed to avoid extending the findings to all people with high triglycerides or nutrient deficiency. - Application exceptions: Do not merge entry TG criteria for people taking and not taking statins. - Remaining uncertainty: Additional details of the full baseline-characteristics table remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S18, S19 ### N07 · Is selection through a prerandomization tolerability run-in verified? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Randomization selected people who tolerated a 4–8-week niacin run-in. This is not the same safety population as all people starting treatment. - Why unverified: The population, duration and safety records verify tolerator selection. Numbers excluded during selection are not thereby verified. - Reason for missing information: Run-in entry/exclusion denominators and reason-specific counts remain unverified. - Required materials and conditions: Run-in participation, reasons for exclusion and flow into randomization. - Materials to obtain first: Run-in participation, reasons for exclusion and flow into randomization. - Further research: Review prerandomization flow and exclusion reasons to distinguish selected participants from all starters. - Conditions for verification: Verify the 4–8-week niacin tolerability run-in and its prerandomization timing. - Why this condition is needed: Needed to avoid extending selected-tolerator findings to efficacy/safety in all first-time starters. - Application exceptions: Do not add the 4–8-week prerandomization run-in to randomized treatment or long-term safety follow-up. - Remaining uncertainty: Run-in entry/exclusion denominators and reason-specific counts remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S18, S19 ### N08 · Are baseline diagnostic values for nutritional niacin deficiency reported? Verification status: Not reported Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: This was not a trial selected for nutritional niacin deficiency. The historical record states that deficiency diagnostic values were not reported within the source material used. - Why unverified: Nonreporting is limited to the accessed scope. It does not establish universal nondeficiency, no subgroup benefit or worldwide absence of data. - Reason for missing information: Baseline deficiency test values and subgroup comparisons are unavailable in this retained scope. - Required materials and conditions: Baseline niacin-deficiency diagnostic criteria and measurements. - Materials to obtain first: Baseline niacin-deficiency diagnostic criteria and measurements. - Further research: If deficiency was defined and measured, link it to prespecified effect-modification analyses. - Conditions for verification: Check whether deficiency tests, criteria and participant-specific values are reported. - Why this condition is needed: Needed to distinguish disease/lipid eligibility from nutritional deficiency status. - Application exceptions: Not selecting for deficiency does not establish that testing confirmed every participant was nondeficient. - Remaining uncertainty: Baseline deficiency test values and subgroup comparisons are unavailable in this retained scope. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S18 ### N09 · Is the chemical ingredient’s manufacturing origin verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Nicotinic acid is a chemical entity, so a botanical part is inapplicable. Actual manufacturing origin remains unverified in the original claim conditions. - Why unverified: Chemical identity is verified, but evidence establishing manufacturing origin is unavailable in the retained scope. - Reason for missing information: Manufacturing-origin documentation is unverified. - Required materials and conditions: Product raw-material and manufacturing-origin documents. - Materials to obtain first: Product raw-material and manufacturing-origin documents. - Further research: Trace ingredient identity and trial product through manufacturing records; separate claims of equivalent products. - Conditions for verification: Check for direct documentation of the NIASPAN ingredient’s manufacturing origin. - Why this condition is needed: Needed to distinguish an inapplicable botanical part from unverified manufacturing information. - Application exceptions: A botanical part is inapplicable to nicotinic acid, but this does not verify manufacturing origin. - Remaining uncertainty: Manufacturing-origin documentation is unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15 ### N10 · Is total niacin exposure, including diet and tryptophan equivalents, verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The trial add-on dose is verified, but total niacin intake including diet and tryptophan equivalents is unconfirmed. - Why unverified: An add-on strategy dose alone cannot establish total nutritional exposure. - Reason for missing information: Total-intake measurements and conversion inputs are unverified. - Required materials and conditions: Measurements of diet, concomitant products and tryptophan equivalents. - Materials to obtain first: Measurements of diet, concomitant products and tryptophan equivalents. - Further research: Separate individual add-on dosing from other intake sources; trace total exposure and compare co-treatment differences. - Conditions for verification: Check for total-exposure data linking diet, concomitant niacin and tryptophan equivalents. - Why this condition is needed: Needed to avoid treating the trial add-on dose as total exposure including diet. - Application exceptions: Do not substitute the product target dose for total intake or infer deficiency status. - Remaining uncertainty: Total-intake measurements and conversion inputs are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17 ### N11 · Are randomization and masking details sufficiently verified for the TG comparison? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Historical body-text extraction records central Internet allocation and double blinding, using low-dose IR niacin for masking. The summary does not verify all sequence-generation/concealment details or masking success. - Why unverified: Some allocation/masking methods are verified, but details and actual success assessments remain incomplete. - Reason for missing information: Sequence-generation/concealment details and masking assessments are unverified. - Required materials and conditions: Sequence generation, central allocation, masking procedures and masking-success assessments. - Materials to obtain first: Sequence generation, central allocation, masking procedures and masking-success assessments. - Further research: Compare planned and reported allocation/masking procedures at the level of the outcome. - Conditions for verification: Verify actual central allocation/masking methods and retain gaps in sequence generation and concealment. - Why this condition is needed: Needed to avoid treating an RCT label as verification of every randomization/masking detail. - Application exceptions: A low-dose active control alone does not establish failed masking. - Remaining uncertainty: Sequence-generation/concealment details and masking assessments are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S19 ### N12 · Are TG measurement procedures and conditions sufficiently verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: An objective blood-TG marker and 2-year percentage change from baseline are verified. Fasting sampling, reagent/laboratory versions and detailed standardization were not verified in this retained summary. - Why unverified: Outcome type and time are verified, but measurement procedures remain incompletely specified. - Reason for missing information: Sampling, laboratory, reagent and measurement-condition details remain unverified. - Required materials and conditions: TG sampling, fasting, laboratory, reagents and measurement procedures. - Materials to obtain first: TG sampling, fasting, laboratory, reagents and measurement procedures. - Further research: Compare measurement timing and methods across groups using the original laboratory plan and records. - Conditions for verification: Verify 2-year TG procedures, sampling conditions, laboratory and comparability between groups. - Why this condition is needed: Needed to avoid assuming objective testing removes differences in timing, sampling or laboratories. - Application exceptions: Do not substitute clinical-event measurement for the TG biomarker. - Remaining uncertainty: Sampling, laboratory, reagent and measurement-condition details remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N13 · Are the 2-year TG assessment, approximately 3-year trial and prerandomization period distinguished? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The page concerns 2-year TG percentage change. Trial stopping after approximately 3 years and the 4–8-week prerandomization run-in are separate periods. - Why unverified: Claim conditions and results distinguish the periods. Persistence outside 2 years is not established. - Reason for missing information: Persistence of the same TG effect beyond 2 years remains separately unverified. - Required materials and conditions: Assessment, trial-stopping and run-in timelines. - Materials to obtain first: Assessment, trial-stopping and run-in timelines. - Further research: Link each outcome visit to its timeline and compare changes for that visit only. - Conditions for verification: Distinguish the 2-year selected outcome from prerandomization and overall trial periods. - Why this condition is needed: Needed to avoid mixing outcome time with overall study duration and creating unsupported persistence claims. - Application exceptions: Do not replace the 2-year TG assessment with the 4–8-week run-in or approximately 3-year trial duration. - Remaining uncertainty: Persistence of the same TG effect beyond 2 years remains separately unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N14 · Are the page TG endpoint and the trial’s 1st (primary)/3rd (tertiary) hierarchy distinguished? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The page endpoint is 2-year TG percentage change. The trial 1st (primary) was a cardiovascular composite; lipids were 3rd (tertiary) protocol objectives. - Why unverified: The source explicitly distinguishes the marker and trial hierarchy. Do not turn TG into 1st (primary) clinical-event success. - Reason for missing information: Complete reconciliation with initial registration is a gap addressed in N22. - Required materials and conditions: Endpoint hierarchy in the original protocol and actual reports. - Materials to obtain first: Endpoint hierarchy in the original protocol and actual reports. - Further research: Compare protocol-version hierarchies with reports while keeping markers and events as separate questions. - Conditions for verification: Link the 1st (primary) cardiovascular composite and 3rd (tertiary) lipid objectives to retained plans/reports. - Why this condition is needed: Needed to avoid presenting the page endpoint as success on the trial 1st (primary) endpoint. - Application exceptions: Lipids being 3rd (tertiary) objectives does not justify deleting the observed TG decrease. - Remaining uncertainty: Complete reconciliation with initial registration is a gap addressed in N22. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S19 ### N15 · Are the reported changes and direction verified for the same 2-year TG outcome? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Retained AIM-HIGH2-year TG changes from baseline were ER −28.6% and control −8.1%. Retain the reported decreases without importing another lipid’s figures. - Why unverified: The arm-level values match the retained calculation and core evidence for the same 2-year TG outcome. This differs from verification of a precise between-group estimate. - Reason for missing information: TG percentage-change estimator, dispersion and analysis denominator remain separately unverified. - Required materials and conditions: Concurrent arm-level TG values from the original table/body text. - Materials to obtain first: Concurrent arm-level TG values from the original table/body text. - Further research: Match arm values to the same outcome, time and population; retain opposing findings as well. - Conditions for verification: Attribute ER −28.6% and control −8.1% to the same 2-year TG report. - Why this condition is needed: Needed to avoid merging within-arm changes, other lipids or different times. - Application exceptions: Verified reported decreases do not establish the mean/median estimator or a formal between-group interval. - Remaining uncertainty: TG percentage-change estimator, dispersion and analysis denominator remain separately unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N16 · Is a formal adjusted between-group TG estimate verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Historical −20.5 percentage points subtracts reported −28.6% and −8.1%. The calculation record explicitly excludes an adjusted causal mean difference, mg/dL difference, ARR or NNT; a formal adjusted TG effect remains unverified. - Why unverified: Descriptive arithmetic is recorded, but the formal adjusted between-group effect asked about remains unverified. - Reason for missing information: The formal TG model, adjusted estimate and corresponding dispersion remain unverified. - Required materials and conditions: TG analysis model, adjustment variables, formal estimate and dispersion. - Materials to obtain first: TG analysis model, adjustment variables, formal estimate and dispersion. - Further research: Define the model’s strategy contrast and review it separately from descriptive arithmetic. - Conditions for verification: Verify the formal model, estimator and effect of interest; distinguish arithmetic subtraction of reported arm values. - Why this condition is needed: Needed to avoid upgrading historical descriptive arithmetic into an adjusted causal mean difference. - Application exceptions: Do not recalculate the retained −20.5 percentage points or convert it to mg/dL, ARR or NNT. - Remaining uncertainty: The formal TG model, adjusted estimate and corresponding dispersion remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N17 · Is the mean/median estimator for TG percentage change verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original calculation records the mean or median estimator for TG percentage change as unconfirmed. - Why unverified: Percentage-change values are available, but evidence defining their mean/median estimator is unavailable. - Reason for missing information: The percentage-change estimator is unverified. - Required materials and conditions: The original definition of aggregation/estimation for TG percentage change. - Materials to obtain first: The original definition of aggregation/estimation for TG percentage change. - Further research: Compare arm-level calculation and aggregation definitions in the original statistics section and tables. - Conditions for verification: Verify the reported percentage-change aggregation/estimation method and its definition. - Why this condition is needed: Needed to avoid assuming a mean effect merely because the result is a percentage. - Application exceptions: Do not fill an unconfirmed estimator with either mean or median. - Remaining uncertainty: The percentage-change estimator is unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N18 · Are the actual arm-specific analysis denominators verified for 2-year TG? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Randomization included 3414 participants,1718 versus 1696. The original denominator explanation and evidence explicitly state that these are not verified 2-year TG analysis counts. - Why unverified: Randomized denominators are known, but the actual 2-year TG analysis denominators cannot be established. - Reason for missing information: Arm-specific 2-year TG analysis n remains unverified. - Required materials and conditions: Arm-specific 2-year TG analysis n, visit attendance, exclusions and flow. - Materials to obtain first: Arm-specific 2-year TG analysis n, visit attendance, exclusions and flow. - Further research: Trace randomization, outcome visits, valid measurements and model-analysis denominators as separate steps. - Conditions for verification: Verify valid arm-specific 2-year TG analysis n and its relationship to exclusions/missingness. - Why this condition is needed: Needed to avoid using randomized counts as the lipid-analysis sample. - Application exceptions: Do not substitute 3414,1718/1696 or event-ITT wording for the TG analysis n. - Remaining uncertainty: Arm-specific 2-year TG analysis n remains unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N19 · Are TG missing-data handling, analysis population and effect of interest verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Details of 2-year TG missing-data handling remain unconfirmed. The source states that event-ITT wording does not prove a lipid ITT analysis without missing data. - Why unverified: Event-analysis terminology alone cannot identify the TG analysis population or missing-data handling. - Reason for missing information: TG missingness, exclusions, imputation and sensitivity analyses are unverified. - Required materials and conditions: TG missing-data methods, model, analysis population and sensitivity analyses. - Materials to obtain first: TG missing-data methods, model, analysis population and sensitivity analyses. - Further research: Link missing/post-discontinuation outcomes to models and examine interpretations under different missingness assumptions. - Conditions for verification: Verify how TG missingness, exclusions and imputation connect the analysis population to the strategy effect. - Why this condition is needed: Needed to avoid turning event-ITT wording into proof of a TG analysis without missing data. - Application exceptions: Medication stopping, follow-up loss and missing tests differ; do not fill missing TG with 0. - Remaining uncertainty: TG missingness, exclusions, imputation and sensitivity analyses are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17 ### N20 · Are the TG between-group CI, change-score SD/SE and precision inputs verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original calculation’s standard error, change-score SD, degrees of freedom, confidence level and interval are all unrecorded. A bounded record notes absent matching dispersion/TG between-group CI in the accessed regulatory tables; do not substitute a cardiovascular HR CI. - Why unverified: The relevant TG interval/dispersion inputs are unverified. This does not claim nonreporting throughout an unread original paper. - Reason for missing information: The relevant TG CI, SD/SE, degrees of freedom and confidence level are unverified. - Required materials and conditions: TG between-group CI, change-score SD/SE, degrees of freedom, confidence level and analysis n. - Materials to obtain first: TG between-group CI, change-score SD/SE, degrees of freedom, confidence level and analysis n. - Further research: Match TG estimators to dispersion in original tables/statistical methods; reject intervals from different outcomes as substitutes. - Conditions for verification: Link the TG interval and matching dispersion/confidence level to the corresponding estimator and denominator. - Why this condition is needed: Needed to avoid replacing TG precision with sample size, significance or a different event HR interval. - Application exceptions: Do not replace unrecorded values with 0 or reconstruct CI/SD from IQR or a threshold P value. - Remaining uncertainty: The relevant TG CI, SD/SE, degrees of freedom and confidence level are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N21 · Can TG importance thresholds be compared with a reported interval? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The source retains the TG decrease with EX(a) because its between-group CI/SD were unconfirmed; it did not relabel it E0 or below MCID. No context-validated TG importance threshold/interval is newly established here. - Why unverified: Reported decreases alone cannot establish importance-threshold attainment or clinical-event benefit. The original EX/grade are historical quotations. - Reason for missing information: A direct comparison of TG importance criteria and a reported interval remains unverified. - Required materials and conditions: Context-specific TG importance criteria, a formal effect interval and clinical-outcome links. - Materials to obtain first: Context-specific TG importance criteria, a formal effect interval and clinical-outcome links. - Further research: Compare importance criteria and intervals separately; assess clinical events through direct event-trial findings. - Conditions for verification: Check for a prespecified TG importance threshold and corresponding interval in this population/strategy. - Why this condition is needed: Needed to avoid equating an observed decrease with MCID attainment or event prevention. - Application exceptions: If importance criteria/CI are unverified, do not relabel the decrease as 0 or below MCID. - Remaining uncertainty: A direct comparison of TG importance criteria and a reported interval remains unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N22 · Is TG plan/analysis/timing agreement verified from initial registration to final report? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The archived protocol is Amendment 6 dated 2011-06-01. Lipids are 3rd (tertiary) objectives and the event 1st (primary) has an amendment history. The historical ClinicalTrials.gov record did not render; complete reconciliation with initial registration is not claimed. - Why unverified: The amended protocol and some hierarchy are verified; complete comparison from initial registration through final TG analysis remains incomplete. - Reason for missing information: Complete initial registration history, TG SAP and reasons for changes are unverified. - Required materials and conditions: Initial registration history, all relevant protocol/SAP versions and final TG reporting. - Materials to obtain first: Initial registration history, all relevant protocol/SAP versions and final TG reporting. - Further research: Compare endpoint, time and analysis changes chronologically across versions to assess agreement. - Conditions for verification: Verify the scope of comparison and reasons for changes across initial registration, protocol versions and final TG analyses. - Why this condition is needed: Needed to avoid treating an archived amended protocol as verification of all initial registration records. - Application exceptions: A historical registry rendering failure does not establish nonregistration or selective reporting. - Remaining uncertainty: Complete initial registration history, TG SAP and reasons for changes are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S19 ### N23 · Are cardiovascular 1st (primary) failure and early stopping kept within their interpretation boundaries? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The retained manuscript states cardiovascular 1st (primary) failure and early stopping. Keep the TG decrease as a separate marker observation without turning it into clinical-event prevention. - Why unverified: Retain unfavorable 1st (primary) findings/stopping separately from the selected TG question. No new clinical-event effect size is calculated. - Reason for missing information: Detailed cardiovascular-event estimates are outside this TG table’s scope. - Required materials and conditions: 1st (primary)-event findings, reasons for early stopping and links to TG results. - Materials to obtain first: 1st (primary)-event findings, reasons for early stopping and links to TG results. - Further research: Review each outcome, analysis and time separately; do not merge discordant marker/event findings. - Conditions for verification: Verify reported cardiovascular 1st (primary) failure/early stopping separately from the TG endpoint. - Why this condition is needed: Needed to avoid hiding unfavorable clinical findings/early stopping behind favorable TG decreases. - Application exceptions: Cardiovascular 1st (primary) failure does not negate the TG decrease; a TG decrease does not establish event prevention. - Remaining uncertainty: Detailed cardiovascular-event estimates are outside this TG table’s scope. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S19 ### N24 · Do 25.4% versus 20.1% refer to study-drug discontinuation? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The reported 25.4% versus 20.1% concern study-drug discontinuation. They are not follow-up attrition,2-year TG missingness or specific adverse-event rates. - Why unverified: The safety record and C17 correction clearly classify the percentages. They do not establish complete follow-up status. - Reason for missing information: Actual reason-specific stopping counts, lipid follow-up retention and missing tests remain unverified. - Required materials and conditions: Original arm-specific drug-discontinuation reasons, follow-up retention and missing-test tables. - Materials to obtain first: Original arm-specific drug-discontinuation reasons, follow-up retention and missing-test tables. - Further research: Link follow-up/measurements after drug stopping; examine adherence and missingness separately. - Conditions for verification: Verify that the percentages describe study-drug discontinuation and separate them from follow-up loss. - Why this condition is needed: Needed to avoid presenting medication stopping as TG analysis attrition, follow-up loss or every-AE incidence. - Application exceptions: Do not derive TG missingness counts or specific adverse-event rates from drug-discontinuation percentages. - Remaining uncertainty: Actual reason-specific stopping counts, lipid follow-up retention and missing tests remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17 ### N25 · Are harm-collection methods and event-specific denominators verified for the same exposure/population? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The FDA 2020 source records pharmacological-regimen harms including flushing and increased liver enzymes, glucose and urate. The current summary does not provide every AIM-HIGH event definition, arm count, time denominator or collection procedure. - Why unverified: General harm types and source are verified, but within-trial event-specific comparisons/denominators remain insufficiently verified. - Reason for missing information: AE definitions, collection, arm counts, exposure time and valid denominators are unverified. - Required materials and conditions: Trial AE collection plan, event-specific arm counts, duration, discontinuation reasons and regulatory documents. - Materials to obtain first: Trial AE collection plan, event-specific arm counts, duration, discontinuation reasons and regulatory documents. - Further research: Compare event definitions, active ascertainment and valid follow-up denominators to distinguish signals from comparative frequencies. - Conditions for verification: Distinguish original definitions, collection, exposure and denominators for flushing, liver enzymes, glucose/urate and other harms. - Why this condition is needed: Needed to distinguish general drug warnings from trial event frequencies and collection data. - Application exceptions: Do not count FDA warnings as independent clinical trials or as all-AE incidence. - Remaining uncertainty: AE definitions, collection, arm counts, exposure time and valid denominators are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N26 · Are the specific tests and conditions for laboratory interference verified? Verification status: Partly verified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The manuscript records specific laboratory interference in FDA 2020 Section 7.6. This retained summary does not verify specific tests, every platform, interference magnitude or a universal stopping interval. - Why unverified: The interference source/location is verified, but specific measurement conditions remain unverified. - Reason for missing information: Test-, platform- and exposure-specific interference details remain unverified. - Required materials and conditions: Section 7.6 tests, interference direction, exposure and measurement conditions. - Materials to obtain first: Section 7.6 tests, interference direction, exposure and measurement conditions. - Further research: Compare test-specific interference by platform, reagent and exposure; separate interference from biological change. - Conditions for verification: Distinguish the FDA 2020 interference location from actual verification of methods/exposure conditions. - Why this condition is needed: Needed to avoid treating an interference warning as every abnormal laboratory result or a treatment effect. - Application exceptions: If test methods are unverified, do not invent interference across every platform or a universal stopping interval. - Remaining uncertainty: Test-, platform- and exposure-specific interference details remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15 ### N27 · Is safety directly verified for all starters, long-term use or other doses? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The 4–8-week tolerability run-in limits generalization to all starters. Fixed FDA 2020 warnings do not establish safety across every dose, long-term use or vulnerable population. - Why unverified: Selected-population records and general warnings cannot establish the extended safety scope. - Reason for missing information: Direct safety data for nontolerators, long-term use, other doses and vulnerable populations are unverified. - Required materials and conditions: Direct harm data for run-in exclusions, unselected populations, other doses and long-term use. - Materials to obtain first: Direct harm data for run-in exclusions, unselected populations, other doses and long-term use. - Further research: Study exposure, follow-up and harms in unselected starters separately and compare them with the selected population. - Conditions for verification: Check direct harm data for run-in nontolerators, other doses, long-term use and vulnerable populations. - Why this condition is needed: Needed to avoid turning selected-tolerator/limited-study findings into a safety guarantee for all starters. - Application exceptions: Unverified safety does not justify deleting TG findings or giving personal dosing instructions. - Remaining uncertainty: Direct safety data for nontolerators, long-term use, other doses and vulnerable populations are unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18 ### N28 · Are the reports linked to the same AIM-HIGH study family? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The direct core evidence is AIM-HIGH-NCT00120289. S15’s AIM-HIGH section, S17 trial paper, S18 official archive and S19 protocol are different materials from the same family. - Why unverified: Study name, registration, titles and used locations identify the same family. Do not count the reports as independent replications. - Reason for missing information: Do not derive an independent participant total from the number of reports. - Required materials and conditions: Trial identity, registration number, report titles and links between trial materials. - Materials to obtain first: Trial identity, registration number, report titles and links between trial materials. - Further research: Map reports to studies, outcomes, times and analyses to avoid double-counting citations within the same family. - Conditions for verification: Link S15 AIM-HIGH data, S17,S18 and S19 to the NCT00120289 family. - Why this condition is needed: Needed to avoid counting the regulatory document, trial paper, official archive and protocol as independent trials. - Application exceptions: Different access routes do not establish independent clinical studies. - Remaining uncertainty: Do not derive an independent participant total from the number of reports. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N29 · Is there an independent study family replicating this exact TG strategy comparison? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The direct evidence and references concern the same AIM-HIGH family. Trials in manufacturer tables are not R2 without verified independent authors/funding; other lipids or durations are not replications of this TG comparison. - Why unverified: A separate independent family for the exact TG comparison was not verified within the retained scope. - Reason for missing information: Independent replication and independence for the exact TG strategy remain unverified. - Required materials and conditions: Independent trial identities, arm-specific TG findings, population and funding records. - Materials to obtain first: Independent trial identities, arm-specific TG findings, population and funding records. - Further research: Classify directness by study family, separate different comparisons and assess replication/heterogeneity. - Conditions for verification: Verify independent families for the same population, ER add-on/IR control and 2-year TG comparison. - Why this condition is needed: Needed to avoid treating other lipids/doses or repeated citations within one family as independent TG replication. - Application exceptions: One currently identified family does not mean 0 studies worldwide, R0 or no effect. - Remaining uncertainty: Independent replication and independence for the exact TG strategy remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N30 · Are funding, product supply and reported analysis involvement identified? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The retained record identifies mixed NHLBI/Abbott support and product supply. Reported sponsor analysis non-involvement does not imply I2. I1 quotes the historical verdict. - Why unverified: The bounded reported support, supply and analysis involvement can be identified. Complete independence is not newly certified. - Reason for missing information: Independent audit of every author’s interests and all roles was not performed. - Required materials and conditions: Funding, product supply, author interests and analysis-role documents. - Materials to obtain first: Funding, product supply, author interests and analysis-role documents. - Further research: Separate funding, drug supply, design, analysis and publication roles when comparing independence. - Conditions for verification: Link NHLBI/Abbott mixed support and product supply to the reported level of involvement. - Why this condition is needed: Needed to avoid treating reported analysis non-involvement as proof of public-only funding or independent replication. - Application exceptions: Interests do not automatically exclude results; absence of interests does not establish absence of bias. - Remaining uncertainty: Independent audit of every author’s interests and all roles was not performed. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S17, S19 ### N31 · Does comprehensive searching, including unpublished trials, rule out selection/publication gaps? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original 2026-09-14 review used web indexes, a provided 3081-record index, related originals and direct publisher/FDA/NHLBI material. Exhaustive PubMed/unpublished-trial searching is not claimed. New searches in this work:0. - Why unverified: A bounded search record exists, but comprehensive searching or exclusion of publication bias is unverified. - Reason for missing information: Comprehensive search strategies, unpublished trials and complete selection records remain unverified. - Required materials and conditions: Original search strategy, selection records and unpublished/registered-result lists. - Materials to obtain first: Original search strategy, selection records and unpublished/registered-result lists. - Further research: Use reproducible question-specific searching, family linkage and selection to review missing reports/selected results. - Conditions for verification: Verify the compared scope of sources, strategy, dates, unpublished material and selected outcomes. - Why this condition is needed: Needed to avoid relabelling historical indexed searches as a current systematic search or absence of publication bias. - Application exceptions: No new search in this work does not mean no research or a failed search. - Remaining uncertainty: Comprehensive search strategies, unpublished trials and complete selection records remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N32 · Are original search/review dates distinguished from the retained-record review? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The original search cutoff is 2026-09-14 and the original verdict review date is also 2026-09-14. The retained-record review date is 2026-10-05. Dedicated evidence-cutoff and reference-specific access-date records are absent. - Why unverified: Actual date records and their absence establish the event-specific scope. Do not fill report-specific access dates from a global date. - Reason for missing information: Actual access dates for individual references remain unverified and unrecorded. - Required materials and conditions: Original date fields, individual access histories and current reading receipts. - Materials to obtain first: Original date fields, individual access histories and current reading receipts. - Further research: Distinguish search, review, access, freeze and application as different dated events. - Conditions for verification: Link the original search-cutoff/review dates and retained-record review date to their actual records separately. - Why this condition is needed: Needed to avoid backdating material-specific original access to a global historical date. - Application exceptions: Do not present an absent dedicated evidence-cutoff field as an existing original record. - Remaining uncertainty: Actual access dates for individual references remain unverified and unrecorded. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N33 · Are retained-summary reading, unread external originals and historical access levels distinguished? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Actual reading concerns the retained summary. Historical records describe S15 regulatory PDF/selected-table screenshots, S17 publisher-indexed body text with unrendered tables, S18 official archive HTML and S19 protocol PDF. External materials were all unattempted, unacquired and unread in this work. - Why unverified: The narrow reading-record condition reflects actual actions. Current external content verification is not thereby complete. - Reason for missing information: External-original comparison was not performed in this work; historical material-specific access dates remain unverified. - Required materials and conditions: Current reading receipts and reference-specific material types, URLs and historical access records. - Materials to obtain first: Current reading receipts and reference-specific material types, URLs and historical access records. - Further research: Match access, acquisition, reading and locations to accurate reader badges and links. - Conditions for verification: Separate actual retained-summary reading from current external access/acquisition/reading not attempted. - Why this condition is needed: Needed to avoid upgrading a URL or historical full-text record into current external reading. - Application exceptions: External access not attempted now is not inaccessibility; retain each historical material type/scope. - Remaining uncertainty: External-original comparison was not performed in this work; historical material-specific access dates remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ### N34 · Are direct TG locations distinguished from other lipids and unavailable shared-correction references? Verification status: Met Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: Direct TG locations are S15 Section 5.1/AIM-HIGH, printed pages 4–5, and S17 Lipid Levels. C11 combines TG/LDL arithmetic; C12 has shared Table 3 wording. C14’s L128 and C16’s S16/LDL −14%/duration discrepancy are not inherited as the direct TG bibliography’s 4 sources. - Why unverified: The boundary between direct TG locations, other lipids and unavailable references is identified. Do not substitute another LDL/Table 3 analysis as this TG result’s location. - Reason for missing information: Separate shared-correction,S16 and L128 materials were not read in this work. - Required materials and conditions: Actual TG locations, full shared corrections and reference-specific identity records. - Materials to obtain first: Actual TG locations, full shared corrections and reference-specific identity records. - Further research: Compare correction-specific endpoint, time and source attribution; retain other-question values/unverified references separately. - Conditions for verification: Identify Section 5.1 as the direct TG location; separate other endpoints and unavailable references. - Why this condition is needed: Needed to avoid inheriting LDL/Table 3,S16 or L128 in shared corrections as evidence for this TG value. - Application exceptions: Do not present references absent from the bibliography or old unavailable files as materials actually read. - Remaining uncertainty: Separate shared-correction,S16 and L128 materials were not read in this work. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17 ### N35 · Are the latest current prescribing document and recommendations verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The FDA document used was revised 09/2020. The latest label/current prescribing guidance was not verified in this work; research doses are not personal dosing instructions. - Why unverified: A fixed historical document does not establish verification of the current version. - Reason for missing information: Direct verification of current labels/recommendations was not performed. - Required materials and conditions: Current prescribing-document version, amendment history and prescribing guidance. - Materials to obtain first: Current prescribing-document version, amendment history and prescribing guidance. - Further research: Compare versions while separately recording actual access/dates, administrative facts and clinical results. - Conditions for verification: Distinguish whether current label versions/recommendations have actually been verified. - Why this condition is needed: Needed to avoid presenting a fixed 2020 document as the latest label or personal prescribing advice. - Application exceptions: Approval differs from proof of clinical efficacy; unverified currency does not erase historical records. - Remaining uncertainty: Direct verification of current labels/recommendations was not performed. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15 ### N36 · Are other formulations, high-TG populations, persistence beyond 2 years and optimal dosing directly verified? Verification status: Unverified Reading scope: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. - Current findings: The findings are limited to AIM-HIGH tolerators, NIASPAN ER add-on versus low-dose IR control and 2-year TG. Generic B3, other formulations, all high-TG populations, optimal dose and persistence beyond 2 years are not directly established. - Why unverified: The source limits generalization outside its scope. Do not delete the selected-question decrease or reclassify it as effect 0. - Reason for missing information: Comparative extensions by formulation, population, dose and long-term duration remain unverified. - Required materials and conditions: Original comparative TG studies by formulation, population, dose and long-term duration. - Materials to obtain first: Original comparative TG studies by formulation, population, dose and long-term duration. - Further research: Define each extension question separately; review direct comparisons, effect modification and persistence. - Conditions for verification: Check direct comparisons for formulations, populations, doses and times outside the selected question. - Why this condition is needed: Needed to avoid extending a fixed-question result across all formulations, populations, doses and durations. - Application exceptions: Do not require every extension study for the narrow TG question. - Remaining uncertainty: Comparative extensions by formulation, population, dose and long-term duration remain unverified. No new effects, intervals, denominators, incidence rates or grades are calculated or adjudicated. - Referenced methods: Existing method principles distinguish population, formulation, dose, time, target-treatment comparator, lipid measurement, denominators, missingness, between-group estimates, intervals, plans, report relationships, funding and harms. Detailed conditions are Chamgap’s own application; they do not impose adjusted analysis on every randomized comparison. - Related sources: S15, S17, S18, S19 ## 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: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained historical record: FDA revised 09/2020 Section 5.1/AIM-HIGH, printed pages 4–5, was used for TG. Retain 2-year TG −28.6% versus −8.1%, randomized 1718/1696 and historical arithmetic −20.5 percentage points. Actual 2-year TG analysis n, formal between-group CI and dispersion are unverified. Sections 2/3 formulation and Sections 5/6 and 7.6 safety/laboratory interference have separate fixed-document scopes. Section 14 Table 3–5 records do not replace this TG location. Record level: Retained records of the same study. External originals were not revalidated in this work; retain each material’s historical access limitations. Independent replication: S15 AIM-HIGH regulatory clinical data, S17 direct trial report, S18 official archive and S19 amended protocol belong to the same AIM-HIGH-NCT00120289 family. Do not count the reports as independent replications or sum participants. No new overall unique-study or participant total is provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | | Historical FDA NIASPAN 2020 prescribing-information PDF and selected table screenshots | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | ### S17 AIM-HIGH Investigators. Niacin in Patients with Low HDL Cholesterol Levels Receiving Intensive Statin Therapy [Official source](https://www.nejm.org/doi/full/10.1056/NEJMoa1107579) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained historical record: AIM-HIGH was a multicentre randomized double-blind target-treatment strategy comparison; 3414 randomized, 1718/1696, with actual 2-year TG analysis n unconfirmed. NIASPAN ER 1500–2000 mg/day versus control containing low-dose IR 100–150 mg/day was added to LDL-targeted statin±ezetimibe titration. The reported 2-year TG −28.6% versus −8.1% is not a formal adjusted effect or CI. Retain cardiovascular 1st (primary) failure, early stopping and study-drug discontinuation 25.4% versus 20.1% separately. NHLBI/Abbott mixed support and product supply do not become independent funding because sponsor analysis non-involvement was reported. Tables and supplementary dispersion did not render during historical indexed-body access. Record level: Retained records of the same study. External originals were not revalidated in this work; retain each material’s historical access limitations. Independent replication: S15 AIM-HIGH regulatory clinical data, S17 direct trial report, S18 official archive and S19 amended protocol belong to the same AIM-HIGH-NCT00120289 family. Do not count the reports as independent replications or sum participants. No new overall unique-study or participant total is provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | | Historical NEJM publisher-indexed body text; tables and supplementary dispersion not rendered | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | ### S18 NHLBI BioLINCC AIM-HIGH study archive [Official source](https://biolincc.nhlbi.nih.gov/studies/aimhigh/) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained historical record: Study Population, Study Design and Outcomes in the official BioLINCC AIM-HIGH archive supported age 45 and older, ASCVD/low-HDL residual dyslipidaemia, a 4–8-week tolerability run-in and statin-dependent entry TG ranges. This is a description of the same AIM-HIGH family, not a new independent TG trial or reading of ClinicalTrials.gov registry results. Record level: Retained records of the same study. External originals were not revalidated in this work; retain each material’s historical access limitations. Independent replication: S15 AIM-HIGH regulatory clinical data, S17 direct trial report, S18 official archive and S19 amended protocol belong to the same AIM-HIGH-NCT00120289 family. Do not count the reports as independent replications or sum participants. No new overall unique-study or participant total is provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | | Historical NHLBI BioLINCC official AIM-HIGH archive HTML | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | ### S19 AIM-HIGH Protocol, Amendment 6, 1 June 2011 [Official source](https://biolincc.nhlbi.nih.gov/media/studies/aimhigh/Protocol.pdf) Materials actually read: The retained Korean/English summaries and case-specific condition/application records were read. External abstracts, full texts, registration, protocols and analysis plans remain unread; access was not attempted. Findings recorded in the summary: Retained historical record: the protocol is Amendment 6, 2011-06-01. Retain the locations used for lipids as 3rd (tertiary) objectives, entry lipid criteria, low-dose IR-niacin control, treatment/product supply and stopping plans. The historical ClinicalTrials.gov record did not render. Access to this protocol does not establish successful registry access or complete agreement from initial registration through final TG analysis. Record level: Retained records of the same study. External originals were not revalidated in this work; retain each material’s historical access limitations. Independent replication: S15 AIM-HIGH regulatory clinical data, S17 direct trial report, S18 official archive and S19 amended protocol belong to the same AIM-HIGH-NCT00120289 family. Do not count the reports as independent replications or sum participants. No new overall unique-study or participant total is provided. | Material | Public availability | Access status | Actually read | Notes | |---|---|---|---|---| | Retained bibliographic/linked summary and historical review record | Internally retained summary | Retained copy acquired; summary read | Stored existing review summary read | The retained summary was acquired and read. This is not an original-byte copy of a clinical full text. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | | Historical AIM-HIGH 2011-06-01 Amendment6 protocol PDF and selected-page screenshots | Current public availability unverified | External access not attempted; not acquired | Not read | The retained external URL is provided. Access, acquisition and reading were not attempted in this work. A summary of historical access records. This does not establish direct external full-text, table, registry or protocol reading, or independent clinical certification in this work. The original search/verdict review date is 2026-09-14 and the case-record review date is 2026-10-05. Historical access dates for individual references are unrecorded. Access levels below are historical records; external access, acquisition and reading were not attempted in this work. | ## 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 method-application records were reused. External originals were not reread and method 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 · Link studies and reports separately; do not omit studies solely because results are unreported. · Retained method-application records were reused. External originals were not reread and method 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 result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting. · Retained method-application records were reused. External originals were not reread and method 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 effect estimates, intervals, importance and applicability. Sample size alone does not determine precision. · Retained method-application records were reused. External originals were not reread and method 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 different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence. · Retained method-application records were reused. External originals were not reread and method content was not reassessed. ## What the statuses mean - Met: The narrow fact, identity, numerical attribution or explicit record asked about is verified within retained material; this is not certification of clinical efficacy, precision or overall safety. - Partly verified: Some required information is verified, but analysis, measurement or version details remain incomplete. - Unverified: The fact or analysis cannot be established from retained material; this does not mean effect0, no research worldwide or a current access failure. - Not reported: Not reported within the specified historical material/section actually accessed; do not extend this to entire unread originals. - Conflicting data: Used for inconsistent reports of the same fact. Different lipids or times are not automatically conflicting TG results. - Not applicable: Used when a specific reason makes the condition inapplicable; not a substitute for unverified or unread. - Inaccessible: A failed actual access attempt must be recorded by material and event; not assigned to external material unattempted in this work. - Review incomplete: Limited to external-original comparison not performed in this work; does not undo completed retained-summary review. ## Change history 2026-10-28 · Public page/materials 1.0. The public view and materials were prepared from the existing 36 items. No new clinical search, verification-state change or scoring was performed.