{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Nicotinic acid (prescription NIASPAN ER tablets added to LDL-targeted statin therapy) × Two-year triglyceride percentage change",
  "language": "en",
  "translation_date": "2026-10-28",
  "criteria_version": "1.0",
  "criteria_date": "2026-10-05",
  "condition_origin": "Chamgap's own application conditions",
  "method_sources": [
    {
      "id": "M03",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03",
      "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13",
      "official_principle": "Clearly record the question, eligibility conditions and reasons for changes; distinguish intervention variants.",
      "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed."
    },
    {
      "id": "M04",
      "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04",
      "section": "§4.5, §4.6.1–4.6.3, MECIR C42",
      "official_principle": "Link studies and reports separately; do not omit studies solely because results are unreported.",
      "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed."
    },
    {
      "id": "M08",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08",
      "section": "§8.1–8.2.3, Table 8.2.a",
      "official_principle": "Fix the result and effect of interest when examining randomization, deviations, missingness, measurement and selective reporting.",
      "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed."
    },
    {
      "id": "M15",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15",
      "section": "§15.2.4, §15.3.1–15.3.3",
      "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.",
      "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed."
    },
    {
      "id": "M19",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19",
      "section": "§19.1.2, §19.2.1–19.2.4",
      "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.",
      "review_level": "Retained method-application records were reused. External originals were not reread and method content was not reassessed."
    }
  ],
  "status_dictionary": {
    "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."
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Evidence condition",
      "question": "Is the independent claim specifically the 2-year TG percentage change?",
      "needed": "The original claim linked to the AIM-HIGH question elements.",
      "role": "Required",
      "role_reason": "Needed to keep a surrogate decrease separate from clinical-event prevention and other lipid results.",
      "application_exception": "Korean/English are languages of the same question; an empty subclaim list does not create new claims.",
      "criterion": "Link the original effect claim, actual intervention, population, comparator and time to the TG question.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare manuscript and trial identities; separate independent claims when question elements differ."
    },
    {
      "item_id": "N02",
      "question_type": "Evidence condition",
      "question": "Is the chemical form, formulation and route actually oral NIASPAN ER tablets?",
      "needed": "Product formulation, ingredient and route records.",
      "role": "Required",
      "role_reason": "Needed to avoid treating generic vitamin B3 or other derivatives as the same intervention.",
      "application_exception": "Nicotinamide, inositol hexanicotinate and no-flush products are different interventions.",
      "criterion": "Link nicotinic acid, NIASPAN ER tablets and the oral route to the retained source identity.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Match product name, chemical form and formulation across drug documents and trial records; analyze other products separately."
    },
    {
      "item_id": "N03",
      "question_type": "Evidence condition",
      "question": "Is the target dose of the selected add-on strategy verified?",
      "needed": "Target titration plan and individual actual dosing/adherence records.",
      "role": "Required",
      "role_reason": "Needed to distinguish target dosing from individually achieved dosing and optimal dose.",
      "application_exception": "The 1500–2000 mg/day target range is not a single fixed dose or the achieved dose of every participant.",
      "criterion": "Verify the selected NIASPAN ER target dose and limit extensions to actual achieved or optimal dose.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Trace arm-specific doses, titration and dosing histories to distinguish target from actual dose."
    },
    {
      "item_id": "N04",
      "question_type": "Evidence condition",
      "question": "Does the control strategy contain low-dose IR niacin?",
      "needed": "Control-tablet composition, dose and masking plan.",
      "role": "Required",
      "role_reason": "Needed to avoid misreading a low-dose active masking ingredient as no treatment or a wholly inactive placebo.",
      "application_exception": "The presence of low-dose IR does not establish equivalent dosing/formulation to ER or a monotherapy comparison.",
      "criterion": "Include IR niacin 50 mg/tablet and 100–150 mg/day in the selected comparison.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare control composition, tablet count and dose with the original plan and intervention records."
    },
    {
      "item_id": "N05",
      "question_type": "Evidence condition",
      "question": "Was background treatment titrated to the same LDL target in both groups?",
      "needed": "Background-drug targets, arm-specific titration and actual doses.",
      "role": "Required",
      "role_reason": "Needed to avoid attributing statin/ezetimibe titration differences solely to fixed-dose NIASPAN.",
      "application_exception": "A common target does not imply identical actual arm doses or require every treatment change to match.",
      "criterion": "Verify simvastatin/ezetimibe ranges and the LDL target; distinguish identical fixed-dose treatment.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare target treatment, co-treatment changes and adherence by arm; define the effect as a strategy contrast."
    },
    {
      "item_id": "N06",
      "question_type": "Evidence condition",
      "question": "Are the selected ASCVD/low-HDL population and entry TG criteria verified?",
      "needed": "Eligibility/exclusion criteria and actual recruited-population characteristics.",
      "role": "Required",
      "role_reason": "Needed to avoid extending the findings to all people with high triglycerides or nutrient deficiency.",
      "application_exception": "Do not merge entry TG criteria for people taking and not taking statins.",
      "criterion": "Verify age 45 and older, established ASCVD/low HDL and statin-dependent entry TG ranges.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare eligibility with baseline characteristics and assess directness for other high-TG populations."
    },
    {
      "item_id": "N07",
      "question_type": "Evidence condition",
      "question": "Is selection through a prerandomization tolerability run-in verified?",
      "needed": "Run-in participation, reasons for exclusion and flow into randomization.",
      "role": "Required",
      "role_reason": "Needed to avoid extending selected-tolerator findings to efficacy/safety in all first-time starters.",
      "application_exception": "Do not add the 4–8-week prerandomization run-in to randomized treatment or long-term safety follow-up.",
      "criterion": "Verify the 4–8-week niacin tolerability run-in and its prerandomization timing.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Review prerandomization flow and exclusion reasons to distinguish selected participants from all starters."
    },
    {
      "item_id": "N08",
      "question_type": "Evidence condition",
      "question": "Are baseline diagnostic values for nutritional niacin deficiency reported?",
      "needed": "Baseline niacin-deficiency diagnostic criteria and measurements.",
      "role": "Supplementary; required for deficiency-subgroup interpretation",
      "role_reason": "Needed to distinguish disease/lipid eligibility from nutritional deficiency status.",
      "application_exception": "Not selecting for deficiency does not establish that testing confirmed every participant was nondeficient.",
      "criterion": "Check whether deficiency tests, criteria and participant-specific values are reported.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "If deficiency was defined and measured, link it to prespecified effect-modification analyses."
    },
    {
      "item_id": "N09",
      "question_type": "Evidence condition",
      "question": "Is the chemical ingredient’s manufacturing origin verified?",
      "needed": "Product raw-material and manufacturing-origin documents.",
      "role": "Supplementary; required for claims of identical manufacturing origin",
      "role_reason": "Needed to distinguish an inapplicable botanical part from unverified manufacturing information.",
      "application_exception": "A botanical part is inapplicable to nicotinic acid, but this does not verify manufacturing origin.",
      "criterion": "Check for direct documentation of the NIASPAN ingredient’s manufacturing origin.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Trace ingredient identity and trial product through manufacturing records; separate claims of equivalent products."
    },
    {
      "item_id": "N10",
      "question_type": "Evidence condition",
      "question": "Is total niacin exposure, including diet and tryptophan equivalents, verified?",
      "needed": "Measurements of diet, concomitant products and tryptophan equivalents.",
      "role": "Supplementary; required for total-exposure interpretation",
      "role_reason": "Needed to avoid treating the trial add-on dose as total exposure including diet.",
      "application_exception": "Do not substitute the product target dose for total intake or infer deficiency status.",
      "criterion": "Check for total-exposure data linking diet, concomitant niacin and tryptophan equivalents.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Separate individual add-on dosing from other intake sources; trace total exposure and compare co-treatment differences."
    },
    {
      "item_id": "N11",
      "question_type": "Evidence condition",
      "question": "Are randomization and masking details sufficiently verified for the TG comparison?",
      "needed": "Sequence generation, central allocation, masking procedures and masking-success assessments.",
      "role": "Required",
      "role_reason": "Needed to avoid treating an RCT label as verification of every randomization/masking detail.",
      "application_exception": "A low-dose active control alone does not establish failed masking.",
      "criterion": "Verify actual central allocation/masking methods and retain gaps in sequence generation and concealment.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare planned and reported allocation/masking procedures at the level of the outcome."
    },
    {
      "item_id": "N12",
      "question_type": "Evidence condition",
      "question": "Are TG measurement procedures and conditions sufficiently verified?",
      "needed": "TG sampling, fasting, laboratory, reagents and measurement procedures.",
      "role": "Required",
      "role_reason": "Needed to avoid assuming objective testing removes differences in timing, sampling or laboratories.",
      "application_exception": "Do not substitute clinical-event measurement for the TG biomarker.",
      "criterion": "Verify 2-year TG procedures, sampling conditions, laboratory and comparability between groups.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare measurement timing and methods across groups using the original laboratory plan and records."
    },
    {
      "item_id": "N13",
      "question_type": "Evidence condition",
      "question": "Are the 2-year TG assessment, approximately 3-year trial and prerandomization period distinguished?",
      "needed": "Assessment, trial-stopping and run-in timelines.",
      "role": "Required",
      "role_reason": "Needed to avoid mixing outcome time with overall study duration and creating unsupported persistence claims.",
      "application_exception": "Do not replace the 2-year TG assessment with the 4–8-week run-in or approximately 3-year trial duration.",
      "criterion": "Distinguish the 2-year selected outcome from prerandomization and overall trial periods.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link each outcome visit to its timeline and compare changes for that visit only."
    },
    {
      "item_id": "N14",
      "question_type": "Evidence condition",
      "question": "Are the page TG endpoint and the trial’s 1st (primary)/3rd (tertiary) hierarchy distinguished?",
      "needed": "Endpoint hierarchy in the original protocol and actual reports.",
      "role": "Required",
      "role_reason": "Needed to avoid presenting the page endpoint as success on the trial 1st (primary) endpoint.",
      "application_exception": "Lipids being 3rd (tertiary) objectives does not justify deleting the observed TG decrease.",
      "criterion": "Link the 1st (primary) cardiovascular composite and 3rd (tertiary) lipid objectives to retained plans/reports.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare protocol-version hierarchies with reports while keeping markers and events as separate questions."
    },
    {
      "item_id": "N15",
      "question_type": "Evidence condition",
      "question": "Are the reported changes and direction verified for the same 2-year TG outcome?",
      "needed": "Concurrent arm-level TG values from the original table/body text.",
      "role": "Required",
      "role_reason": "Needed to avoid merging within-arm changes, other lipids or different times.",
      "application_exception": "Verified reported decreases do not establish the mean/median estimator or a formal between-group interval.",
      "criterion": "Attribute ER −28.6% and control −8.1% to the same 2-year TG report.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Match arm values to the same outcome, time and population; retain opposing findings as well."
    },
    {
      "item_id": "N16",
      "question_type": "Evidence condition",
      "question": "Is a formal adjusted between-group TG estimate verified?",
      "needed": "TG analysis model, adjustment variables, formal estimate and dispersion.",
      "role": "Required",
      "role_reason": "Needed to avoid upgrading historical descriptive arithmetic into an adjusted causal mean difference.",
      "application_exception": "Do not recalculate the retained −20.5 percentage points or convert it to mg/dL, ARR or NNT.",
      "criterion": "Verify the formal model, estimator and effect of interest; distinguish arithmetic subtraction of reported arm values.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Define the model’s strategy contrast and review it separately from descriptive arithmetic."
    },
    {
      "item_id": "N17",
      "question_type": "Evidence condition",
      "question": "Is the mean/median estimator for TG percentage change verified?",
      "needed": "The original definition of aggregation/estimation for TG percentage change.",
      "role": "Required",
      "role_reason": "Needed to avoid assuming a mean effect merely because the result is a percentage.",
      "application_exception": "Do not fill an unconfirmed estimator with either mean or median.",
      "criterion": "Verify the reported percentage-change aggregation/estimation method and its definition.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare arm-level calculation and aggregation definitions in the original statistics section and tables."
    },
    {
      "item_id": "N18",
      "question_type": "Evidence condition",
      "question": "Are the actual arm-specific analysis denominators verified for 2-year TG?",
      "needed": "Arm-specific 2-year TG analysis n, visit attendance, exclusions and flow.",
      "role": "Required",
      "role_reason": "Needed to avoid using randomized counts as the lipid-analysis sample.",
      "application_exception": "Do not substitute 3414,1718/1696 or event-ITT wording for the TG analysis n.",
      "criterion": "Verify valid arm-specific 2-year TG analysis n and its relationship to exclusions/missingness.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Trace randomization, outcome visits, valid measurements and model-analysis denominators as separate steps."
    },
    {
      "item_id": "N19",
      "question_type": "Evidence condition",
      "question": "Are TG missing-data handling, analysis population and effect of interest verified?",
      "needed": "TG missing-data methods, model, analysis population and sensitivity analyses.",
      "role": "Required",
      "role_reason": "Needed to avoid turning event-ITT wording into proof of a TG analysis without missing data.",
      "application_exception": "Medication stopping, follow-up loss and missing tests differ; do not fill missing TG with 0.",
      "criterion": "Verify how TG missingness, exclusions and imputation connect the analysis population to the strategy effect.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link missing/post-discontinuation outcomes to models and examine interpretations under different missingness assumptions."
    },
    {
      "item_id": "N20",
      "question_type": "Evidence condition",
      "question": "Are the TG between-group CI, change-score SD/SE and precision inputs verified?",
      "needed": "TG between-group CI, change-score SD/SE, degrees of freedom, confidence level and analysis n.",
      "role": "Required",
      "role_reason": "Needed to avoid replacing TG precision with sample size, significance or a different event HR interval.",
      "application_exception": "Do not replace unrecorded values with 0 or reconstruct CI/SD from IQR or a threshold P value.",
      "criterion": "Link the TG interval and matching dispersion/confidence level to the corresponding estimator and denominator.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Match TG estimators to dispersion in original tables/statistical methods; reject intervals from different outcomes as substitutes."
    },
    {
      "item_id": "N21",
      "question_type": "Evidence condition",
      "question": "Can TG importance thresholds be compared with a reported interval?",
      "needed": "Context-specific TG importance criteria, a formal effect interval and clinical-outcome links.",
      "role": "Supplementary; required for importance/clinical-benefit interpretation",
      "role_reason": "Needed to avoid equating an observed decrease with MCID attainment or event prevention.",
      "application_exception": "If importance criteria/CI are unverified, do not relabel the decrease as 0 or below MCID.",
      "criterion": "Check for a prespecified TG importance threshold and corresponding interval in this population/strategy.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare importance criteria and intervals separately; assess clinical events through direct event-trial findings."
    },
    {
      "item_id": "N22",
      "question_type": "Evidence condition",
      "question": "Is TG plan/analysis/timing agreement verified from initial registration to final report?",
      "needed": "Initial registration history, all relevant protocol/SAP versions and final TG reporting.",
      "role": "Required",
      "role_reason": "Needed to avoid treating an archived amended protocol as verification of all initial registration records.",
      "application_exception": "A historical registry rendering failure does not establish nonregistration or selective reporting.",
      "criterion": "Verify the scope of comparison and reasons for changes across initial registration, protocol versions and final TG analyses.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare endpoint, time and analysis changes chronologically across versions to assess agreement."
    },
    {
      "item_id": "N23",
      "question_type": "Evidence condition",
      "question": "Are cardiovascular 1st (primary) failure and early stopping kept within their interpretation boundaries?",
      "needed": "1st (primary)-event findings, reasons for early stopping and links to TG results.",
      "role": "Supplementary; required for clinical-event interpretation",
      "role_reason": "Needed to avoid hiding unfavorable clinical findings/early stopping behind favorable TG decreases.",
      "application_exception": "Cardiovascular 1st (primary) failure does not negate the TG decrease; a TG decrease does not establish event prevention.",
      "criterion": "Verify reported cardiovascular 1st (primary) failure/early stopping separately from the TG endpoint.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Review each outcome, analysis and time separately; do not merge discordant marker/event findings."
    },
    {
      "item_id": "N24",
      "question_type": "Evidence condition",
      "question": "Do 25.4% versus 20.1% refer to study-drug discontinuation?",
      "needed": "Original arm-specific drug-discontinuation reasons, follow-up retention and missing-test tables.",
      "role": "Supplementary; required for adherence/safety interpretation",
      "role_reason": "Needed to avoid presenting medication stopping as TG analysis attrition, follow-up loss or every-AE incidence.",
      "application_exception": "Do not derive TG missingness counts or specific adverse-event rates from drug-discontinuation percentages.",
      "criterion": "Verify that the percentages describe study-drug discontinuation and separate them from follow-up loss.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Link follow-up/measurements after drug stopping; examine adherence and missingness separately."
    },
    {
      "item_id": "N25",
      "question_type": "Evidence condition",
      "question": "Are harm-collection methods and event-specific denominators verified for the same exposure/population?",
      "needed": "Trial AE collection plan, event-specific arm counts, duration, discontinuation reasons and regulatory documents.",
      "role": "Supplementary; required for comparative-harm/frequency interpretation",
      "role_reason": "Needed to distinguish general drug warnings from trial event frequencies and collection data.",
      "application_exception": "Do not count FDA warnings as independent clinical trials or as all-AE incidence.",
      "criterion": "Distinguish original definitions, collection, exposure and denominators for flushing, liver enzymes, glucose/urate and other harms.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare event definitions, active ascertainment and valid follow-up denominators to distinguish signals from comparative frequencies."
    },
    {
      "item_id": "N26",
      "question_type": "Evidence condition",
      "question": "Are the specific tests and conditions for laboratory interference verified?",
      "needed": "Section 7.6 tests, interference direction, exposure and measurement conditions.",
      "role": "Supplementary; required for laboratory-interference interpretation",
      "role_reason": "Needed to avoid treating an interference warning as every abnormal laboratory result or a treatment effect.",
      "application_exception": "If test methods are unverified, do not invent interference across every platform or a universal stopping interval.",
      "criterion": "Distinguish the FDA 2020 interference location from actual verification of methods/exposure conditions.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare test-specific interference by platform, reagent and exposure; separate interference from biological change."
    },
    {
      "item_id": "N27",
      "question_type": "Evidence condition",
      "question": "Is safety directly verified for all starters, long-term use or other doses?",
      "needed": "Direct harm data for run-in exclusions, unselected populations, other doses and long-term use.",
      "role": "Supplementary; required for safety-scope extensions",
      "role_reason": "Needed to avoid turning selected-tolerator/limited-study findings into a safety guarantee for all starters.",
      "application_exception": "Unverified safety does not justify deleting TG findings or giving personal dosing instructions.",
      "criterion": "Check direct harm data for run-in nontolerators, other doses, long-term use and vulnerable populations.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Study exposure, follow-up and harms in unselected starters separately and compare them with the selected population."
    },
    {
      "item_id": "N28",
      "question_type": "Evidence condition",
      "question": "Are the reports linked to the same AIM-HIGH study family?",
      "needed": "Trial identity, registration number, report titles and links between trial materials.",
      "role": "Required",
      "role_reason": "Needed to avoid counting the regulatory document, trial paper, official archive and protocol as independent trials.",
      "application_exception": "Different access routes do not establish independent clinical studies.",
      "criterion": "Link S15 AIM-HIGH data, S17,S18 and S19 to the NCT00120289 family.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Map reports to studies, outcomes, times and analyses to avoid double-counting citations within the same family."
    },
    {
      "item_id": "N29",
      "question_type": "Evidence condition",
      "question": "Is there an independent study family replicating this exact TG strategy comparison?",
      "needed": "Independent trial identities, arm-specific TG findings, population and funding records.",
      "role": "Supplementary; required for independent-replication claims",
      "role_reason": "Needed to avoid treating other lipids/doses or repeated citations within one family as independent TG replication.",
      "application_exception": "One currently identified family does not mean 0 studies worldwide, R0 or no effect.",
      "criterion": "Verify independent families for the same population, ER add-on/IR control and 2-year TG comparison.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Classify directness by study family, separate different comparisons and assess replication/heterogeneity."
    },
    {
      "item_id": "N30",
      "question_type": "Evidence condition",
      "question": "Are funding, product supply and reported analysis involvement identified?",
      "needed": "Funding, product supply, author interests and analysis-role documents.",
      "role": "Supplementary; required for independence interpretation",
      "role_reason": "Needed to avoid treating reported analysis non-involvement as proof of public-only funding or independent replication.",
      "application_exception": "Interests do not automatically exclude results; absence of interests does not establish absence of bias.",
      "criterion": "Link NHLBI/Abbott mixed support and product supply to the reported level of involvement.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Separate funding, drug supply, design, analysis and publication roles when comparing independence."
    },
    {
      "item_id": "N31",
      "question_type": "Evidence condition",
      "question": "Does comprehensive searching, including unpublished trials, rule out selection/publication gaps?",
      "needed": "Original search strategy, selection records and unpublished/registered-result lists.",
      "role": "Supplementary; required for claims of overall evidence completeness",
      "role_reason": "Needed to avoid relabelling historical indexed searches as a current systematic search or absence of publication bias.",
      "application_exception": "No new search in this work does not mean no research or a failed search.",
      "criterion": "Verify the compared scope of sources, strategy, dates, unpublished material and selected outcomes.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Use reproducible question-specific searching, family linkage and selection to review missing reports/selected results."
    },
    {
      "item_id": "N32",
      "question_type": "Evidence condition",
      "question": "Are original search/review dates distinguished from the retained-record review?",
      "needed": "Original date fields, individual access histories and current reading receipts.",
      "role": "Required (verification-scope record)",
      "role_reason": "Needed to avoid backdating material-specific original access to a global historical date.",
      "application_exception": "Do not present an absent dedicated evidence-cutoff field as an existing original record.",
      "criterion": "Link the original search-cutoff/review dates and retained-record review date to their actual records separately.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Distinguish search, review, access, freeze and application as different dated events."
    },
    {
      "item_id": "N33",
      "question_type": "Evidence condition",
      "question": "Are retained-summary reading, unread external originals and historical access levels distinguished?",
      "needed": "Current reading receipts and reference-specific material types, URLs and historical access records.",
      "role": "Required (reading record)",
      "role_reason": "Needed to avoid upgrading a URL or historical full-text record into current external reading.",
      "application_exception": "External access not attempted now is not inaccessibility; retain each historical material type/scope.",
      "criterion": "Separate actual retained-summary reading from current external access/acquisition/reading not attempted.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Match access, acquisition, reading and locations to accurate reader badges and links."
    },
    {
      "item_id": "N34",
      "question_type": "Evidence condition",
      "question": "Are direct TG locations distinguished from other lipids and unavailable shared-correction references?",
      "needed": "Actual TG locations, full shared corrections and reference-specific identity records.",
      "role": "Required",
      "role_reason": "Needed to avoid inheriting LDL/Table 3,S16 or L128 in shared corrections as evidence for this TG value.",
      "application_exception": "Do not present references absent from the bibliography or old unavailable files as materials actually read.",
      "criterion": "Identify Section 5.1 as the direct TG location; separate other endpoints and unavailable references.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare correction-specific endpoint, time and source attribution; retain other-question values/unverified references separately."
    },
    {
      "item_id": "N35",
      "question_type": "Evidence condition",
      "question": "Are the latest current prescribing document and recommendations verified?",
      "needed": "Current prescribing-document version, amendment history and prescribing guidance.",
      "role": "Supplementary; required for current-prescribing interpretation",
      "role_reason": "Needed to avoid presenting a fixed 2020 document as the latest label or personal prescribing advice.",
      "application_exception": "Approval differs from proof of clinical efficacy; unverified currency does not erase historical records.",
      "criterion": "Distinguish whether current label versions/recommendations have actually been verified.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Compare versions while separately recording actual access/dates, administrative facts and clinical results."
    },
    {
      "item_id": "N36",
      "question_type": "Evidence condition",
      "question": "Are other formulations, high-TG populations, persistence beyond 2 years and optimal dosing directly verified?",
      "needed": "Original comparative TG studies by formulation, population, dose and long-term duration.",
      "role": "Supplementary; required for extension claims",
      "role_reason": "Needed to avoid extending a fixed-question result across all formulations, populations, doses and durations.",
      "application_exception": "Do not require every extension study for the narrow TG question.",
      "criterion": "Check direct comparisons for formulations, populations, doses and times outside the selected question.",
      "basis": "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.",
      "condition_origin": "Conditions for the NIASPAN ER add-on, low-dose IR control and 2-year TG strategy comparison were developed with knowledge of retained content and frozen before application. This does not establish clinical preregistration, blinded development, official-method certification or independent clinical validation.",
      "proposed_research": "Define each extension question separately; review direct comparisons, effect modification and persistence."
    }
  ]
}