{
  "schema_version": "chamgap-public-evidence-check-1.0",
  "public_id": "v3092-main",
  "verdict_number": "3092",
  "title": "Oral NIASPAN extended-release nicotinic acid — added to usual diabetes care × HbA1c increase in adults with stable type 2 diabetes and dyslipidemia",
  "view_version": "1.0",
  "view_created_date": "2026-11-01",
  "criteria_version": "NGM-v3092-NIASPAN-HBA1C-INCREASE-1.0",
  "criteria_date": "2026-10-05",
  "review_date": "2026-10-05",
  "legacy_evidence_date": "2026-09-15",
  "review_scope": {
    "materials_read": "Retained Korean and English manuscripts and case-specific criteria and application records",
    "clinical_papers_directly_read": false,
    "new_clinical_search": false,
    "limitation": "No external clinical abstracts, full texts, registrations or analysis plans were newly read. Historical access records are distinguished from the retained summaries read in this review. The original judgment, numerical values and unverified information are preserved; no new searches, calculations or reassessment were performed.",
    "date_meaning": "This is the date on which the retained materials were checked, not the date of a search for the latest clinical literature."
  },
  "claim_context": {
    "population": "Age 21 or older, with stable type 2 diabetes and dyslipidemia; HbA1c ≤9%, fasting glucose ≤200 mg/dL; deficiency status unverified",
    "intervention": "NIASPAN (Kos) single-ingredient extended-release (ER) oral tablets; separate salt designation, batch and excipients unverified",
    "dose": "Target of 1500 mg/day at bedtime; titration through 375→500→750→1000 mg/day, followed by 1500 mg/day",
    "comparator": "Addition of matching placebo; common policy for diet and adjustable diabetes medication; existing statin users continued treatment, without statins being common treatment for everyone",
    "endpoint": "Between-group difference in change from baseline to week 16 in HbA1c (%p); the trial's primary (1st) safety endpoint",
    "duration": "Total of 16 weeks, including 4 weeks of titration; target dose during weeks 5–16",
    "excluded_extensions": "Do not extend this to reduced efficacy, a general safety-only flag (safety_only), all niacin formulations, FPG/incident diabetes/lipids/FMD/cardiovascular events, long-term complications, individual risk rates or an optimal dose."
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Which population, intervention, comparator, time period and endpoint define the comparative harm claim?",
      "needed": "Material linking the identity of the current claim with the actual population, intervention, comparator, endpoint and time point",
      "role": "Required",
      "role_reason": "Needed to distinguish the quantitative harm claim of an HbA1c increase from glycemic-improvement efficacy and a general safety indicator.",
      "application_exception": "Do not change the clinical-harm/increase classification (clinical_harm_claim/increase) to reduced efficacy or a safety-only flag (safety_only), or include other niacin interventions or other clinical endpoints.",
      "criterion": "The actual original material specifies the boundaries: stable type 2 diabetes and dyslipidemia, adjustable usual care, NIASPAN ER added versus matching placebo, and change over a total of 16 weeks in HbA1c.",
      "basis": "C01: Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C04: M03 §3.2.1; detailed population criteria are internally designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H09: Chamgap's own interpretive boundaries. The M19 principles are referenced; no official causality tool was applied. Reason for adapting this to comparative HbA1c harm: needed to distinguish the quantitative harm claim of an HbA1c increase from glycemic-improvement efficacy and a general safety indicator. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the current manuscript with the trial's actual comparison, and record the reason and the scope before and after any boundary change.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The selected original claim concerns adults with stable type 2 diabetes and dyslipidemia and an increase in HbA1c. It is a quantitative harm question comparing the oral NIASPAN ER add-on strategy with matching placebo over a total of 16 weeks.",
      "condition_status": "Met",
      "status_reason": "The actual claim identity and comparison scope are verified. This status does not establish the clinical importance of the increase or harm from all niacin interventions.",
      "missingness": "There is no gap in the boundaries of the current separate question; detailed analyses and long-term extensions are considered under separate criteria.",
      "uncertainty": "There is no gap in the boundaries of the current separate question; detailed analyses and long-term extensions are considered under separate criteria. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Material linking the identity of the current claim with the actual population, intervention, comparator, endpoint and time point"
    },
    {
      "item_id": "N02",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the actual ingredient, product, release formulation and route verified?",
      "needed": "The core trial's product name, ingredient, release formulation and route, and the corresponding locations in the official product description",
      "role": "Required",
      "role_reason": "Needed to avoid transferring results for NIASPAN extended-release nicotinic acid to nicotinamide or IR/SR formulations.",
      "application_exception": "Do not resolve an unverified separate salt designation by assuming equivalence to another salt. Distinguish the null value/not_applicable status for plant-part information (botanical_part) from the unverified manufacturing origin.",
      "criterion": "The original material distinguishes the single active ingredient nicotinic acid, NIASPAN (Kos), ER oral tablets, and the excluded molecules/formulations.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Reason for adapting this to comparative HbA1c harm: needed to avoid transferring results for NIASPAN extended-release nicotinic acid to nicotinamide or IR/SR formulations. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the trial product's ingredient and release formulation with the original description, and consider other molecules/formulations only through their own direct evidence.",
      "current_reports": [
        "S01",
        "S06"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The intervention is NIASPAN (Kos), single-ingredient nicotinic acid in ER oral tablets. Nicotinamide, NR, NMN, no-flush preparations, nicotine and IR/SR substitutes are not treated as the same intervention. Equivalence of a separate salt was not verified.",
      "condition_status": "Met",
      "status_reason": "The selected ingredient, product, release formulation, route and exclusions are verified. This does not mean that the manufacturing process, batch or excipients have also been verified.",
      "missingness": "The separate salt, manufacturing batch and exact excipients remain unverified, separately from this product-identity verification.",
      "uncertainty": "The separate salt, manufacturing batch and exact excipients remain unverified, separately from this product-identity verification. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The core trial's product name, ingredient, release formulation and route, and the corresponding locations in the official product description"
    },
    {
      "item_id": "N03",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Is the actual information on manufacturing origin, batch and excipients verified?",
      "needed": "Specifications for the trial product's manufacturing process, raw-material origin, batch and excipients",
      "role": "Supplementary; required for detailed product identity",
      "role_reason": "Knowing a product name and knowing its actual manufacturing origin, batch and excipients are different levels of information.",
      "application_exception": "Although plant-part information is not applicable to this chemical ingredient, do not change the unverified/null manufacturing origin to Not applicable.",
      "criterion": "Direct material is available to verify the selected product's manufacturing origin, batch and excipients.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed. Reason for adapting this to comparative HbA1c harm: knowing a product name and knowing its actual manufacturing origin, batch and excipients are different levels of information. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "If permitted product material is obtained, compare it with the trial batch and do not inherit information from another product.",
      "current_reports": [
        "S01",
        "S06"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The raw material's manufacturing origin, such as synthesis or fermentation, the batch and the exact excipients are unverified. Plant-part information has a null value/not_applicable status, whereas manufacturing origin has a null value/unverified status; these are different.",
      "condition_status": "Unverified",
      "status_reason": "The retained material does not provide evidence that establishes the product's detailed manufacturing information. Do not erase this gap by using the Not applicable designation for this chemical ingredient's plant-part information.",
      "missingness": "Specifications for the actual manufacturing origin, trial batch and excipients are needed.",
      "uncertainty": "Specifications for the actual manufacturing origin, trial batch and excipients are needed. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Specifications for the trial product's manufacturing process, raw-material origin, batch and excipients"
    },
    {
      "item_id": "N04",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the trial's diagnosis, stability, age and inclusion/exclusion criteria verified?",
      "needed": "Inclusion/exclusion criteria, diagnosis, baseline-characteristics table and material verifying stability",
      "role": "Required",
      "role_reason": "Needed to avoid applying the selected trial's results unchanged to people with diabetes generally or to healthy people.",
      "application_exception": "Keep participants' baseline niacin-deficiency status separately unverified, and do not invent detailed subgroup effects.",
      "criterion": "The original material specifies age 21 or older, stable type 2 diabetes and dyslipidemia, diagnoses, entry criteria, sex and major exclusions.",
      "basis": "C04: M03 §3.2.1; detailed population criteria are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Reason for adapting this to comparative HbA1c harm: needed to avoid applying the selected trial's results unchanged to people with diabetes generally or to healthy people. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the actual recruited population's diagnoses and entry criteria with the claim's target population, and keep direct results in other populations separate.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Participants were men and women aged 21 or older with stable type 2 diabetes and dyslipidemia. Two measurements showed HbA1c ≤ 9% and fasting glucose ≤ 200 mg/dL. Exclusions recorded included relevant liver disease, a history of gout or peptic ulcer, and thiazolidinedione use.",
      "condition_status": "Met",
      "status_reason": "This verifies the population and entry criteria specified in the original material. It does not verify the magnitude of harm in all people with diabetes or in excluded vulnerable groups.",
      "missingness": "Detailed subgroups, representativeness and deficiency status fall within a separate evidence scope.",
      "uncertainty": "Detailed subgroups, representativeness and deficiency status fall within a separate evidence scope. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Inclusion/exclusion criteria, diagnosis, baseline-characteristics table and material verifying stability"
    },
    {
      "item_id": "N05",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are baseline niacin status, deficiency classification and total dietary intake verified?",
      "needed": "Baseline niacin measurements, deficiency-classification criteria and data on total dietary niacin",
      "role": "Supplementary; required for interpreting deficiency/total exposure",
      "role_reason": "Needed to avoid treating deficiency correction and prescription-drug addition in nondeficient participants as the same question.",
      "application_exception": "Do not extend information not identified in the text accessed at the time into a claim that it was unreported throughout the entire paper, or into evidence that deficiency was absent.",
      "criterion": "Participant-specific data are available on baseline niacin measurement, deficiency classification and total dietary intake.",
      "basis": "C04: M03 §3.2.1; detailed population criteria are internally designed / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Reason for adapting this to comparative HbA1c harm: needed to avoid treating deficiency correction and prescription-drug addition in nondeficient participants as the same question. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Review direct material while distinguishing baseline status from drug and dietary exposure, and treat results of deficiency treatment as a separate question.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Baseline niacin concentrations, deficiency classification and total dietary niacin could not be verified in the text accessed at the time. This trial is not defined as a deficiency-treatment trial.",
      "condition_status": "Not reported",
      "status_reason": "The original record of unknowns specifies the scope as not_reported_in_accessed_text. The external full text was not read in this review, so this is not extended to nonreporting throughout the current full text.",
      "missingness": "Baseline niacin/dietary information beyond what was verified at the time, and its exact original locations, are unavailable.",
      "uncertainty": "Baseline niacin/dietary information beyond what was verified at the time, and its exact original locations, are unavailable. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Baseline niacin measurements, deficiency-classification criteria and data on total dietary niacin"
    },
    {
      "item_id": "N06",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the actual planned titration, target dose and dosing frequency verified?",
      "needed": "Trial treatment schedule, target dose, tablet count and data on actual adherence/dose reached",
      "role": "Required",
      "role_reason": "Needed to avoid displaying the target dose as a fixed dose actually taken throughout the entire period.",
      "application_exception": "The study schedule is not a personal dosing instruction, and actual adherence/doses reached are distinguished from the planned titration schedule.",
      "criterion": "Bedtime administration at 1 dose per 1 day, weekly titration, target dose and tablet count are linked to the actual plan.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed. Reason for adapting this to comparative HbA1c harm: needed to avoid displaying the target dose as a fixed dose actually taken throughout the entire period. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare planned administration with actual treatment histories, distinguishing nominal dose, dose reached and cumulative exposure.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The schedule was 1 dose per 1 day at bedtime, titrated through week 1 at 375 mg/day, week 2 at 500 mg/day, week 3 at 750 mg/day and week 4 at 1,000 mg/day, followed by a target for weeks 5–16 of 1,500 mg/day. The target tablet count was recorded as two 750 mg tablets.",
      "condition_status": "Met",
      "status_reason": "The nominal plan in the original treatment schedule is verified. This does not verify that every participant actually maintained this dose.",
      "missingness": "Individual adherence, target doses reached and change histories remain separately unverified.",
      "uncertainty": "Individual adherence, target doses reached and change histories remain separately unverified. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Trial treatment schedule, target dose, tablet count and data on actual adherence/dose reached"
    },
    {
      "item_id": "N07",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the titration period, target-dose period and total follow-up period separately identified and verified?",
      "needed": "Schedules for treatment, titration, target-dose maintenance and end of follow-up, together with long-term follow-up material",
      "role": "Required",
      "role_reason": "Needed to avoid turning the total of 16 weeks into fixed exposure to the target of 1,500 mg/day for 16 weeks, or into long-term follow-up.",
      "application_exception": "Do not use the planned 12-week target-dose period as a new clinical minimum duration or long-term safety criterion.",
      "criterion": "The planned total of 16 weeks, 4 weeks of titration and target dose in weeks 5–16 are distinguished from the absence of long-term follow-up.",
      "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed / H08: M19 §19.1.2–19.2.4; internal application. Reason for adapting this to comparative HbA1c harm: needed to avoid turning the total of 16 weeks into fixed exposure to the target of 1,500 mg/day for 16 weeks, or into long-term follow-up. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Link the timeline to actual exposure and measurement schedules, and examine persistence after discontinuation or long-term outcomes through separate follow-up.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The planned total treatment of 16 weeks includes 4 weeks of titration, and the target-dose period is 12 weeks. Long-term follow-up for the selected HbA1c question has no recorded value (null).",
      "condition_status": "Met",
      "status_reason": "The actual planned timeline is specified. The 16-week results do not verify persistence, rare harms or long-term complications.",
      "missingness": "Persistence of effects after discontinuation and follow-up for long-term harms remain separately unverified.",
      "uncertainty": "Persistence of effects after discontinuation and follow-up for long-term harms remain separately unverified. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Schedules for treatment, titration, target-dose maintenance and end of follow-up, together with long-term follow-up material"
    },
    {
      "item_id": "N08",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Is the actual composition of the matching placebo verified?",
      "needed": "Material on placebo manufacture, composition, appearance, corresponding tablets and blinding assessment",
      "role": "Required",
      "role_reason": "Needed to avoid turning the term matching placebo into verification of its exact ingredients or complete blinding.",
      "application_exception": "Do not use unverified placebo details as evidence that there was no placebo or as confirmation that blinding failed.",
      "criterion": "The matching placebo and a direct description of its composition, appearance and whether it contained active ingredients are verified.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application. Reason for adapting this to comparative HbA1c harm: needed to avoid turning the term matching placebo into verification of its exact ingredients or complete blinding. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the placebo description with the trial product, distinguishing the unverified details of composition and blinding.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "There is a record of a randomized, double-blind comparison using matching placebo. Its exact composition beyond the description of matching placebo is unverified.",
      "condition_status": "Partly verified",
      "status_reason": "The comparison type is verified, but details of the actual composition, appearance and establishment of blinding were not verified.",
      "missingness": "The placebo's exact composition and appearance, and blinding-assessment material, are unavailable.",
      "uncertainty": "The placebo's exact composition and appearance, and blinding-assessment material, are unavailable. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Material on placebo manufacture, composition, appearance, corresponding tablets and blinding assessment"
    },
    {
      "item_id": "N09",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the common policies on diabetes-treatment adjustment, statins and aspirin verified?",
      "needed": "Trial rules for common care, diabetes-medication adjustment, statins and permitted aspirin use",
      "role": "Required",
      "role_reason": "Needed to distinguish a common policy from a claim that everyone actually received identical concomitant medication.",
      "application_exception": "Do not automatically judge diabetes-medication adjustment as contamination or design failure; preserve it as the care policy in the comparison of this add-on strategy.",
      "criterion": "Permission to change usual diabetes care, continuation of existing statins, the absence of a statin requirement for everyone, and the policy permitting but not requiring aspirin are verified.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application. Reason for adapting this to comparative HbA1c harm: needed to distinguish a common policy from a claim that everyone actually received identical concomitant medication. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Distinguish the common care policy from actual medication changes, include that policy in the effect of interest, and examine how departures by arm were handled.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Under the common diet and diabetes-care policy, diabetes medications could be increased or added. Only existing statin users continued statins; they were not common treatment given to everyone. Other lipid-lowering medications underwent washout, and aspirin to prevent flushing was permitted but was not mandatory common treatment.",
      "condition_status": "Met",
      "status_reason": "The care policy in the original comparison is specified. This does not mean that actual concomitant medications, doses or times of addition were the same for every participant.",
      "missingness": "Details of the treatment changes actually made in each arm are considered under the next criterion.",
      "uncertainty": "Details of the treatment changes actually made in each arm are considered under the next criterion. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Trial rules for common care, diabetes-medication adjustment, statins and permitted aspirin use"
    },
    {
      "item_id": "N10",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the actual concomitant-treatment adjustments, adherence, rescue treatment and their analytical handling verified for each arm?",
      "needed": "Histories of changes to diabetes medications, statins and aspirin by arm, together with adherence, rescue-treatment and information on how these were handled in the analysis",
      "role": "Required",
      "role_reason": "Needed to avoid turning the observed add-on strategy into an isolated drug contribution under completely fixed diabetes medication.",
      "application_exception": "The existence of a policy permitting changes does not establish that the extent of changes by arm, adherence or the adjustment model was also verified.",
      "criterion": "Actual data verify concomitant-medication changes, attainment of the target dose, adherence/discontinuation and the corresponding analytical handling for each arm.",
      "basis": "H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / E04: M08 §8.2.2, M15 §15.3.1; internal application. Reason for adapting this to comparative HbA1c harm: needed to avoid turning the observed add-on strategy into an isolated drug contribution under completely fixed diabetes medication. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare actual treatment changes with the effect of interest for the add-on strategy, and examine how departures and adjustments by arm were handled in the analysis.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original record states that actual concomitant medications were not identical for everyone and that diabetes-medication adjustment was included in the comparison's care policy for the add-on strategy. The extent of changes by individual and arm, adherence to the target dose and detailed handling of rescue treatment were not verified.",
      "condition_status": "Partly verified",
      "status_reason": "Differences in concomitant treatment and permission to adjust treatment are verified, but the detailed data and analytical implications were not sufficiently verified.",
      "missingness": "Gaps remain in the extent and timing of actual medication changes by arm, adherence, and their detailed handling in the analytical model.",
      "uncertainty": "Gaps remain in the extent and timing of actual medication changes by arm, adherence, and their detailed handling in the analytical model. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Histories of changes to diabetes medications, statins and aspirin by arm, together with adherence, rescue-treatment and information on how these were handled in the analysis"
    },
    {
      "item_id": "N11",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the actual methods for randomization, allocation concealment and baseline balance verified?",
      "needed": "The original randomization-sequence and allocation-concealment procedures, and the baseline-characteristics table by arm",
      "role": "Required; interpretation of comparative harm",
      "role_reason": "The labels RCT and double-blind alone cannot establish that sequence generation, concealment and selection differences have been addressed.",
      "application_exception": "Do not turn unverified concealment into actual absence of concealment or a confirmed bias defect. No new RoB grade is issued.",
      "criterion": "Material is available to verify the parallel-group design, random-sequence generation, allocation concealment and baseline balance.",
      "basis": "E01: M08 §8.1–8.2.3; internal application / H05: Design considerations in M19 §19.2.2–19.2.4; detailed recording of confounding is internally designed. Reason for adapting this to comparative HbA1c harm: the labels RCT and double-blind alone cannot establish that sequence generation, concealment and selection differences have been addressed. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the allocation process with actual baseline balance, distinguishing verified methods from remaining gaps.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "ADVENT is a randomized, double-blind, matching-placebo-controlled parallel-group trial. Details of sequence generation and allocation concealment are recorded as unverified.",
      "condition_status": "Partly verified",
      "status_reason": "The design and reports of randomization/blinding are verified, but methodological details are lacking. Do not reuse the original B2 as a new bias judgment.",
      "missingness": "Details of sequence generation, allocation concealment and baseline balance for the selected comparison are needed.",
      "uncertainty": "Details of sequence generation, allocation concealment and baseline balance for the selected comparison are needed. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The original randomization-sequence and allocation-concealment procedures, and the baseline-characteristics table by arm"
    },
    {
      "item_id": "N12",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the definition, units, analysis time point and endpoint hierarchy for HbA1c verified?",
      "needed": "Material on the HbA1c outcome definition, units, time point and endpoint hierarchy, and their correspondence with the original plan",
      "role": "Required",
      "role_reason": "Needed to avoid reading the primary (1st) safety endpoint, HbA1c, as a secondary lipid result, diagnostic event or incidence rate.",
      "application_exception": "Keep the reported primary (1st) hierarchy separate from whether its prospective registration plan has been verified.",
      "criterion": "The between-group difference in change from baseline to week 16 in HbA1c, the %p unit, and its status as the original trial's primary (1st) safety endpoint are distinguished.",
      "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application / E06: M08 Table 8.2.a, M04 §4.6.3; internal application. Reason for adapting this to comparative HbA1c harm: needed to avoid reading the primary (1st) safety endpoint, HbA1c, as a secondary lipid result, diagnostic event or incidence rate. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the selected outcome's change, between-group direction and hierarchy with the original results, and consider other endpoints separately.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "HbA1c is the original trial's primary (1st) safety endpoint and the current page's sole priority outcome. The outcome of interest is the between-group difference in change from baseline to week 16, in %p.",
      "condition_status": "Met",
      "status_reason": "The endpoint, hierarchy, time point and measure are verified in the retained original text. This status does not verify prospective agreement with the registration/SAP or an increase in clinical events.",
      "missingness": "The exact assay and comparison with prospective plans remain separately unverified.",
      "uncertainty": "The exact assay and comparison with prospective plans remain separately unverified. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Material on the HbA1c outcome definition, units, time point and endpoint hierarchy, and their correspondence with the original plan"
    },
    {
      "item_id": "N13",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the actual laboratory measuring HbA1c and the scheduled visit times verified?",
      "needed": "The original testing schedule, laboratory and participant-specific records of completed measurements",
      "role": "Required",
      "role_reason": "Needed to distinguish repeated measurement time points from the single end-of-study outcome and clarify which follow-up period the result belongs to.",
      "application_exception": "Do not turn scheduled measurement times into a claim that completion/analysis data for every participant have been obtained.",
      "criterion": "The original material specifies the central laboratory and measurements at baseline and weeks 4·8·12·16.",
      "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H02: Design-specific harm questions in M19 §19.2; details of temporal relationships are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application. Reason for adapting this to comparative HbA1c harm: needed to distinguish repeated measurement time points from the single end-of-study outcome and clarify which follow-up period the result belongs to. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Link scheduled measurements with actual completion records and examine the denominator at each time point.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "HbA1c was scheduled to be assessed at the central laboratory at baseline and weeks 4·8·12·16. The denominators for actual completed measurements at each time point are unverified.",
      "condition_status": "Met",
      "status_reason": "The criterion for verifying the laboratory and schedule is met. This is not extended to verification of analysis denominators, assay standardization or handling of missing data.",
      "missingness": "Separate material is needed for completion denominators at each time point and the exact assay.",
      "uncertainty": "Separate material is needed for completion denominators at each time point and the exact assay. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The original testing schedule, laboratory and participant-specific records of completed measurements"
    },
    {
      "item_id": "N14",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the HbA1c assay method, equipment, standardization and interference assessment verified?",
      "needed": "Specifications for the central laboratory's HbA1c method, equipment, standardization, quality control and interference assessment",
      "role": "Required",
      "role_reason": "The description of a central laboratory alone cannot guarantee measurement standardization or the absence of interference by arm.",
      "application_exception": "Do not turn unverified assay details into invalidity of the entire result or confirmation of assay interference.",
      "criterion": "Material is available to verify the exact HbA1c method, equipment and standardization, and interference/measurement limitations by arm.",
      "basis": "H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / E03: M08 Table 8.2.a, M03 §3.2.4; internal application. Reason for adapting this to comparative HbA1c harm: the description of a central laboratory alone cannot guarantee measurement standardization or the absence of interference by arm. No new clinical causality/grade judgment or official methodological procedure was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare assay conditions with collection at each time point, and examine whether evidence of measurement differences or interference actually exists.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Beyond the information that a central laboratory was used, the exact HbA1c assay method, equipment, standardization and assay-interference assessment are unverified.",
      "condition_status": "Unverified",
      "status_reason": "Detailed specifications needed to compare the selected HbA1c difference with measurement conditions have not been obtained.",
      "missingness": "Direct original source locations for the assay method, equipment, standardization and interference assessment are unavailable.",
      "uncertainty": "Direct original source locations for the assay method, equipment, standardization and interference assessment are unavailable. No new clinical effect, risk rate, individual response or grade is calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Specifications for the central laboratory's HbA1c method, equipment, standardization, quality control and interference assessment"
    },
    {
      "item_id": "N15",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the overall assigned/treated counts and selected-arm counts distinguished from the HbA1c analysis denominator?",
      "needed": "An arm-specific flow table for allocation, treatment, completion and endpoint analysis, and the original basis for the labels used",
      "role": "Required",
      "role_reason": "Needed to avoid substituting the overall sample or treated-arm counts for the analysis denominator of the selected HbA1c outcome.",
      "application_exception": "Preserve the original bytes of the structured group-count field name randomized_arm_counts and the manuscript's description of the treated groups; do not reinterpret them as the actual endpoint analysis n.",
      "criterion": "The overall counts of 148 assigned and 146 treated participants, the selected-arm counts of 52/49, and the unverified endpoint-specific analysis n are each explicitly distinguished.",
      "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for specific designs were developed internally / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / E04: M08 §8.2.2, M15 §15.3.1; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid substituting the overall sample or treated-arm counts for the analysis denominator of the selected HbA1c outcome. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the stage represented by each sample count with the outcome denominator, and record the overall, selected, and analysis populations separately.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Overall, 148 participants were randomized; the authors' ITT/treated population, excluding those who received no treatment, comprised 146 participants. The selected-arm counts of 52/49 are not HbA1c analysis denominators. The structured field randomized_arm_counts=[52,49] is also retained under its original name.",
      "condition_status": "Met",
      "status_reason": "The retained manuscript clearly distinguishes each stage from the missing analysis n. This does not mean that the endpoint analysis denominator itself has been verified.",
      "missingness": "The HbA1c analysis n and the arm-specific links across stages are gaps addressed by the following condition.",
      "uncertainty": "The HbA1c analysis n and the arm-specific links across stages are gaps addressed by the following condition. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "An arm-specific flow table for allocation, treatment, completion and endpoint analysis, and the original basis for the labels used"
    },
    {
      "item_id": "N16",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the endpoint-specific HbA1c analysis n, handling of missing data, and variance of paired changes been verified?",
      "needed": "Endpoint-specific n by arm, reasons for and handling of missing data, individual repeated measurements, and change-variance data",
      "role": "Required",
      "role_reason": "This is needed to avoid filling in analysis denominators, variances, or intervals from the selected-arm counts of 52/49 and a rounded P value.",
      "application_exception": "Preserve the original missing values. Do not substitute arm-specific end-of-study SEs for change SD/SE or perform new calculations.",
      "criterion": "The HbA1c analysis n, handling of missing data, and SD/SE of paired changes for the selected comparison are linked to original data.",
      "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for specific designs were developed internally / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / E04: M08 §8.2.2, M15 §15.3.1; internal application / E05: M15 §15.3.1–15.3.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid filling in analysis denominators, variances, or intervals from the selected-arm counts of 52/49 and a rounded P value. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the analysis populations, missing data at each time point, and variance of paired changes with the original results tables; do not fill unverified information through calculation.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The HbA1c analysis n=[null,null], change SD=[null,null], and SE=null. Endpoint-specific handling of missing data and variance of paired changes are also unverified.",
      "condition_status": "Unverified",
      "status_reason": "The exact outcome denominators, missing-data information, and paired variances have not been obtained. The counts 52/49, 146, and 148 do not replace them.",
      "missingness": "Endpoint n, handling of missing data, and variance of paired changes are needed.",
      "uncertainty": "Endpoint n, handling of missing data, and variance of paired changes are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Endpoint-specific n by arm, reasons for and handling of missing data, individual repeated measurements, and change-variance data"
    },
    {
      "item_id": "N17",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have losses to follow-up, their reasons, and their effects on the endpoint been verified for the selected comparison?",
      "needed": "A table linking reasons and timing of attrition/discontinuation by arm with HbA1c missingness and its handling",
      "role": "Required",
      "role_reason": "This is needed to avoid treating reported attrition and HbA1c missingness as the same event, or applying the original historical rate as a new bias score.",
      "application_exception": "The expression 17/101=16.83% is an existing record and is not recalculated. Original scoring criteria such as 15% or 200 participants are not imposed as adequacy criteria for the new conditions.",
      "criterion": "Attrition counts, reasons by arm, timing, and their links to HbA1c missingness and its analytical impact are verified for the selected comparison.",
      "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for specific designs were developed internally / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid treating reported attrition and HbA1c missingness as the same event, or applying the original historical rate as a new bias score. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Track treatment discontinuation, loss to follow-up, and missing measurements separately to assess which data remain for the selected outcome.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original bias record retains attrition of 17/101=16.83% for the selected comparison. Detailed links between reasons/timing by arm and HbA1c missingness/handling are unverified.",
      "condition_status": "Partly verified",
      "status_reason": "Historical attrition figures are available, but endpoint missingness and analytical impact have not been verified. The existing B2 is not used as a score for the new review status.",
      "missingness": "Reasons by arm, timing, and the impact of endpoint missingness are unverified.",
      "uncertainty": "Reasons by arm, timing, and the impact of endpoint missingness are unverified. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "A table linking reasons and timing of attrition/discontinuation by arm with HbA1c missingness and its handling"
    },
    {
      "item_id": "N18",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Does the authors' ITT designation agree with the actual effect of interest and analysis population?",
      "needed": "Analysis plan, inclusion/exclusion rules, between-group model, and definition of the effect of interest",
      "role": "Required",
      "role_reason": "This is needed to avoid treating a population that excludes untreated participants as ITT based on all randomized participants.",
      "application_exception": "Retain the authors' ITT wording while distinguishing it from actual exclusions and the effect of interest. Do not infer an adherence effect or an adjusted model.",
      "criterion": "Agreement is verified between the effect of assignment overall or the actual effect of interest and the analysis inclusion/exclusion rules and model.",
      "basis": "E04: M08 §8.2.2, M15 §15.3.1; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid treating a population that excludes untreated participants as ITT based on all randomized participants. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the authors' designation with the actual analysis population to distinguish the add-on strategy's effect of interest, adherence effects, and the effects of exclusions.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The authors describe the 146 treated participants as ITT but excluded participants who received no treatment. The selected HbA1c analysis n and exact model are unverified. The comparison is read as an add-on strategy under adjustable diabetes care.",
      "condition_status": "Partly verified",
      "status_reason": "The designation and exclusion of untreated participants are verified, but agreement with ITT based on all assigned participants and a formal between-group model cannot be established.",
      "missingness": "Details of inclusion/exclusion, the model, and the effect of interest for the endpoint analysis are needed.",
      "uncertainty": "Details of inclusion/exclusion, the model, and the effect of interest for the endpoint analysis are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Analysis plan, inclusion/exclusion rules, between-group model, and definition of the effect of interest"
    },
    {
      "item_id": "N19",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Has attribution of the reported arm-specific HbA1c changes, P value, and existing arithmetic difference been verified?",
      "needed": "Arm-specific mean changes, the reported between-group test, a formal model-estimate table, and the original arithmetic record",
      "role": "Required",
      "role_reason": "This is needed to avoid turning the changes in both arms, the P value, and the arithmetic difference into different analyses or clinical risk rates.",
      "application_exception": "The original +0.31 %p is reused solely as historical arithmetic; no formal model estimate, formal CI, or individual risk rate is generated.",
      "criterion": "The selected comparison's +0.29 versus −0.02 %p, reported P=.048, and existing arithmetic +0.31 %p are each linked to their original locations and the nature of their analyses.",
      "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to the specific question were developed internally / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / E04: M08 §8.2.2, M15 §15.3.1; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid turning the changes in both arms, the P value, and the arithmetic difference into different analyses or clinical risk rates. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Link reported values to outcomes, time points, and analyses, distinguishing descriptive arithmetic from formal estimates without repeating the calculation.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The arm-specific mean changes are +0.29 versus −0.02 %p, and the reported between-group P=0.048. The existing arithmetic difference of +0.31 %p remains designated reported_arm_changes_arithmetic_only; it is not a formal adjusted-model estimate.",
      "condition_status": "Met",
      "status_reason": "The sources and analytical nature of the reported values and existing arithmetic value are verified. This is not verification of the magnitude of clinical risk or a formal CI.",
      "missingness": "The formal between-group estimate, CI, and variance are gaps addressed by the following condition.",
      "uncertainty": "The formal between-group estimate, CI, and variance are gaps addressed by the following condition. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Arm-specific mean changes, the reported between-group test, a formal model-estimate table, and the original arithmetic record"
    },
    {
      "item_id": "N20",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the formal between-group HbA1c change estimate, SE, and CI been verified?",
      "needed": "A formal between-group change-estimate table, model, paired variance, denominator, and confidence interval",
      "role": "Required",
      "role_reason": "This is needed to avoid establishing the magnitude and precision of harm from significance or a simple mean difference alone.",
      "application_exception": "Do not reconstruct an interval or standardized effect using the rounded P=.048, end-of-study SEs, or 52/49.",
      "criterion": "The formal between-group change estimate and SE/CI appropriate to the selected comparison, time point, and analysis are verified from the original results.",
      "basis": "C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for specific designs were developed internally / E04: M08 §8.2.2, M15 §15.3.1; internal application / E05: M15 §15.3.1–15.3.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid establishing the magnitude and precision of harm from significance or a simple mean difference alone. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Link the formal estimate and interval to the verified analysis to examine compatible magnitudes, leaving unverified information unverified.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The interval field and the standard error field (standard_error) in the retained calculation are null. A confidence interval for the formal between-group change estimate could not be verified from the original data, and +0.31 %p is only an arithmetic difference.",
      "condition_status": "Unverified",
      "status_reason": "The estimate, interval, and variance for the formal change contrast cannot be verified. Do not fill them in from the reported P value alone.",
      "missingness": "The formal estimate, SE/CI, and corresponding analysis/denominator are needed.",
      "uncertainty": "The formal estimate, SE/CI, and corresponding analysis/denominator are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "A formal between-group change-estimate table, model, paired variance, denominator, and confidence interval"
    },
    {
      "item_id": "N21",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the matching prospective registration, protocol, SAP, and handling of multiplicity been verified?",
      "needed": "The matching ADVENT registration, original protocol, SAP, and information on analysis changes/multiplicity",
      "role": "Required",
      "role_reason": "This is needed to avoid treating a reported primary (1st) endpoint as completed verification against the planned analysis.",
      "application_exception": "A null registration_id and an unobtained plan do not establish that the study was unregistered or selectively reported. Do not attach another registration or protocol to ADVENT.",
      "criterion": "Agreement or changes in endpoints, time points, models, and multiplicity between the matching prospective ADVENT plan and actual results can be verified.",
      "basis": "C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid treating a reported primary (1st) endpoint as completed verification against the planned analysis. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the prospective plan with the results by endpoint, time point, and analysis, leaving unobtained information unverified.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The matching registration number, original protocol, and analysis plan are unverified, and registration_id and S01 nct are null. The exact multiplicity adjustment for the selected comparison has also not been verified.",
      "condition_status": "Unverified",
      "status_reason": "Insufficient material is available to verify comparison with the prospective plan and the handling of multiplicity. This does not mean that absence of registration or actual selective reporting has been established.",
      "missingness": "Planning, history, and multiplicity-handling information corresponding to ADVENT are needed.",
      "uncertainty": "Planning, history, and multiplicity-handling information corresponding to ADVENT are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The matching ADVENT registration, original protocol, SAP, and information on analysis changes/multiplicity"
    },
    {
      "item_id": "N22",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Has a validated threshold for the clinical importance of this HbA1c difference been identified?",
      "needed": "A validated importance threshold, paired variance, and patient-importance information for this HbA1c comparison",
      "role": "Required; interpretation of magnitude",
      "role_reason": "This is needed to distinguish an increase signal from the magnitude of clinically important deterioration.",
      "application_exception": "Do not turn EX into no numerical value, no effect, or failure to meet a threshold, and do not invent an arbitrary MCID, minimum n, or duration.",
      "criterion": "An important-difference threshold or a justified interpretation of the corresponding standardized effect appropriate to this population, add-on strategy, and duration is verified.",
      "basis": "E05: M15 §15.3.1–15.3.3; internal application / H09: Chamgap's own interpretive boundaries. The M19 principles are referenced; no official causality tool was applied. Reason for adapting this to the comparative HbA1c harm question: This is needed to distinguish an increase signal from the magnitude of clinically important deterioration. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Interpret verified evidence on importance against the formal change estimate/interval; do not replace an importance threshold with conventional significance alone.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "An increase signal exists, but its clinical magnitude could not be judged because a validated clinical-importance threshold, variance of paired changes, and formal interval are unavailable. The original EX means that clinical magnitude remains undetermined.",
      "condition_status": "Unverified",
      "status_reason": "A justified importance threshold and corresponding statistical information are lacking. The original P value and arithmetic +0.31 %p alone do not establish the magnitude of important harm.",
      "missingness": "Context-specific evidence on importance, paired variance, and a formal interval are needed.",
      "uncertainty": "Context-specific evidence on importance, paired variance, and a formal interval are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "A validated importance threshold, paired variance, and patient-importance information for this HbA1c comparison"
    },
    {
      "item_id": "N23",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "For the 1,000 mg arm in the same ADVENT trial, have the HbA1c difference and uncertainty been verified?",
      "needed": "The 1,000 mg arm's HbA1c results, between-group estimate/interval, and denominator in the same trial",
      "role": "Supplementary; required for interpreting dose-related/opposing findings",
      "role_reason": "This is needed to avoid turning another dose in the same trial into independent replication or evidence of safety at all lower doses.",
      "application_exception": "Do not interpret nonsignificance at P=.16 as an effect of 0, equivalence, a harmless dose, or an established dose–response relationship.",
      "criterion": "For the 1,000 mg arm, the actual between-group HbA1c difference, denominator, and interval are verified and distinguished from the selected 1,500 mg comparison.",
      "basis": "C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was developed internally / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / E08: M03 §3.2.1–3.2.4; details of dose, persistence, and effect modification were developed internally / H07: M04 §4.6.1–4.6.2; adaptation for harm data was developed internally. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid turning another dose in the same trial into independent replication or evidence of safety at all lower doses. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the actual results and analyses by dose, retaining them as context from the same family; do not newly calculate direct dose effects or a harmless-dose threshold.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The 1,000 mg/day arm in the same ADVENT trial did not establish a significant difference from placebo, with P=0.16. It is not counted as independent replication, and the current retained summary lacks the complete difference, denominator, and CI for that comparison.",
      "condition_status": "Partly verified",
      "status_reason": "The report of a nonsignificant test is verified, but the full between-group effect magnitude and uncertainty have not been verified.",
      "missingness": "Complete results, denominators, and a formal interval for that dose arm are needed.",
      "uncertainty": "Complete results, denominators, and a formal interval for that dose arm are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The 1,000 mg arm's HbA1c results, between-group estimate/interval, and denominator in the same trial"
    },
    {
      "item_id": "N24",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "For the 1,000 mg arm, does baseline HbA1c agree between the table and abstract?",
      "needed": "The corresponding value in the original Table 1 and abstract, and any correction or author explanation",
      "role": "Supplementary; required for verifying a conflict concerning the same fact",
      "role_reason": "This is needed to avoid arbitrarily correcting conflicting values or claiming that they have been reconciled as different endpoints.",
      "application_exception": "Do not treat successful documentation of a conflict as fulfillment of the data-consistency condition. Do not change values for the currently selected arms.",
      "criterion": "For the same 1,000 mg arm, baseline HbA1c agrees between the table and abstract, or the difference is resolved by evidence of a correction.",
      "basis": "C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was developed internally / E03: M08 Table 8.2.a, M03 §3.2.4; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid arbitrarily correcting conflicting values or claiming that they have been reconciled as different endpoints. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the original locations for the same fact side by side; resolve differences only when correction evidence is available, retaining the previous values.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "For the same 1,000 mg arm, baseline HbA1c is recorded as 7.23% in the table and 7.28% in the abstract; it was not arbitrarily corrected.",
      "condition_status": "Conflicting information",
      "status_reason": "Reports of the same baseline value actually disagree. Successful preservation of the conflict is distinguished from verification of data consistency.",
      "missingness": "An original correction, author explanation, or additional context distinguishing the values is needed.",
      "uncertainty": "An original correction, author explanation, or additional context distinguishing the values is needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The corresponding value in the original Table 1 and abstract, and any correction or author explanation"
    },
    {
      "item_id": "N25",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Has the original material for the no-change conference presentation cited by the study report been verified?",
      "needed": "The original conference abstract, presentation identity, population/intervention, results, and trial-linkage information",
      "role": "Supplementary; required for interpreting replication/opposing evidence",
      "role_reason": "This is needed to avoid elevating the study report's secondhand citation to a newly read independent presentation result.",
      "application_exception": "Do not assign a unique trial count or participant count to a presentation whose relationship to the same trial or another family is unverified.",
      "criterion": "Material is available to directly verify the identity, population, intervention, HbA1c results, and family relationships of the original presentation.",
      "basis": "C02: M04 §4.6.1–4.6.2: distinction between studies and reports; internal application to cohort/outcome linkage / C03: M04 §4.5–4.6: data-collection/selection principles; the distinction between access and reading and the hyperlink conventions were developed internally / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was developed internally / H07: M04 §4.6.1–4.6.2; adaptation for harm data was developed internally. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid elevating the study report's secondhand citation to a newly read independent presentation result. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Verify the relationship between the original presentation and study report to distinguish same-family, different-family, and unknown relationships; do not count a secondhand citation as independent replication.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original study report states that a conference presentation found no HbA1c change. That original presentation could not be directly verified, and the 13 bibliographic records (citation) do not contain a separate presentation identity.",
      "condition_status": "Unverified",
      "status_reason": "The included document contains a secondhand citation, but the actual material, family, and results of the original presentation have not been verified.",
      "missingness": "The identity and content of the original presentation and its family links are needed.",
      "uncertainty": "The identity and content of the original presentation and its family links are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The original conference abstract, presentation identity, population/intervention, results, and trial-linkage information"
    },
    {
      "item_id": "N26",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the actual formulation, comparison, timing, and between-group HbA1c results of ADMIT been verified?",
      "needed": "ADMIT treatment/run-in, factorial co-interventions, diabetic-subgroup results tables, denominators, tests/intervals, and corrections",
      "role": "Supplementary; required for interpreting indirect/opposing comparisons",
      "role_reason": "This is needed to avoid turning within-arm maintenance in IR ADMIT into a null between-group effect for NIASPAN ER or replication of the exact comparison.",
      "application_exception": "Retain the ADMIT abstract/table P-value discrepancy as originally recorded; do not newly fill in figures absent from the current retained version.",
      "criterion": "The IR formulation, different dose/run-in/population, time point of interest, between-group results, and uncertainty in ADMIT are verified.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations were developed internally / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to the specific question were developed internally / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was developed internally / E04: M08 §8.2.2, M15 §15.3.1; internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid turning within-arm maintenance in IR ADMIT into a null between-group effect for NIASPAN ER or replication of the exact comparison. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare formulation, population, co-interventions, and the effect of interest over time to distinguish within-arm from between-arm results; do not count them together as direct ER comparisons.",
      "current_reports": [
        "S02"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "ADMIT compares a different IR Niacor formulation, dose, run-in, factorial co-interventions, and population/time-specific effect of interest. HbA1c was maintained within the nicotinic acid arm, while it declined in the placebo arm. The original record also preserves an abstract/table P-value discrepancy, but the current retained summary does not contain the specific figures.",
      "condition_status": "Partly verified",
      "status_reason": "The direction and design differences of the indirect comparison are verified, but the complete between-group estimate, denominator, uncertainty, and details of the P-value conflict are lacking.",
      "missingness": "The complete ADMIT results tables, denominators, and original locations of the test discrepancy are needed.",
      "uncertainty": "The complete ADMIT results tables, denominators, and original locations of the test discrepancy are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "ADMIT treatment/run-in, factorial co-interventions, diabetic-subgroup results tables, denominators, tests/intervals, and corrections"
    },
    {
      "item_id": "N27",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the actual release formulation, measurements, and period-specific contrasts in the Garg crossover trial been verified?",
      "needed": "The product release formulation, assay method, crossover sequence/periods, paired results, and denominators in the original Garg full text",
      "role": "Supplementary; required for interpreting indirect evidence",
      "role_reason": "This is needed to avoid automatically equating the nicotinic acid name and glycosylated hemoglobin results with the selected ER HbA1c change.",
      "application_exception": "Do not calculate the 13-participant crossover trial as an independent-arm design or treat glycosylated hemoglobin as a verified equivalent HbA1c assay.",
      "criterion": "The crossover trial's release formulation, measurement method, paired period comparison, and denominator/interval are verified.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations were developed internally / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to the specific question were developed internally / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for specific designs were developed internally / E04: M08 §8.2.2, M15 §15.3.1; internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid automatically equating the nicotinic acid name and glycosylated hemoglobin results with the selected ER HbA1c change. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Examine the actual periods and paired contrasts in the crossover design and assay equivalence; do not calculate an independent-arm effect.",
      "current_reports": [
        "S03"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The PubMed abstract record describes a 13-participant crossover trial, 1 dose of 1.5 g taken three times daily, 8 weeks per period, and a relative increase in glycosylated hemoglobin. The release formulation and equivalence to the selected HbA1c assay are unverified.",
      "condition_status": "Partly verified",
      "status_reason": "Abstract-level information on design, administration, and direction is available, but the formulation, assay equivalence, and complete paired analysis have not been verified.",
      "missingness": "The release formulation, assay method, crossover analysis, and formal results in the original full text are needed.",
      "uncertainty": "The release formulation, assay method, crossover analysis, and formal results in the original full text are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The product release formulation, assay method, crossover sequence/periods, paired results, and denominators in the original Garg full text"
    },
    {
      "item_id": "N28",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have the ingredient, product, and comparison in the report of improvement with low-dose niacin and sitagliptin been verified?",
      "needed": "Ingredient/product specifications, sitagliptin/chromium arm composition, comparator, and HbA1c results tables for the Karim trial",
      "role": "Supplementary; required for determining the applicability of opposing evidence",
      "role_reason": "This is needed to retain results in the opposite direction while preventing findings with a different dose and co-treatment from being repurposed for the selected prescription ER comparison.",
      "application_exception": "Do not fill in NIASPAN for the unverified nicotinic acid/amide identity and product of the 14 mg/day niacin.",
      "criterion": "The actual molecule, product, dose, co-treatment arms, comparator, and comparative scope of the HbA1c results are verified.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations were developed internally / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to the specific question were developed internally / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses was developed internally / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H03: M19 §19.2.2–19.2.4, M03 §3.2.3; internal application. Reason for adapting this to the comparative HbA1c harm question: This is needed to retain results in the opposite direction while preventing findings with a different dose and co-treatment from being repurposed for the selected prescription ER comparison. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare the molecule, product, co-treatment, comparator, and direction of results, preserving them separately from the selected comparison.",
      "current_reports": [
        "S04"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The study of low-dose niacin 14 mg/day combined with sitagliptin reported improvement. The exact nicotinic acid/amide identity and product, including its release formulation, are unverified, and this differs from the NIASPAN ER 1,500 mg/day comparison.",
      "condition_status": "Partly verified",
      "status_reason": "The favorable direction and the difference in low-dose co-treatment are verified, but the actual ingredient, product, and complete comparative estimate have not been sufficiently verified.",
      "missingness": "The exact molecule, product, arm composition, and results tables are needed.",
      "uncertainty": "The exact molecule, product, arm composition, and results tables are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Ingredient/product specifications, sitagliptin/chromium arm composition, comparator, and HbA1c results tables for the Karim trial"
    },
    {
      "item_id": "N29",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Has evidence of independent replication of the exact NIASPAN comparison been verified?",
      "needed": "Links between unique trials and reports, and independent results tables, for the exact comparison",
      "role": "Supplementary; required for interpreting replication/generalizability",
      "role_reason": "This is needed to avoid counting reports of the same dose arms, regulatory secondhand citations, reviews, or registrations as independent replication trials.",
      "application_exception": "Preserve the original R1 and the single direct family. Do not newly judge the number of studies worldwide, the total number of unique participants, or the absence of replication.",
      "criterion": "Results from an independent family matching the product, dose, population, policy, time point, and HbA1c comparison are directly verified.",
      "basis": "C02: M04 §4.6.1–4.6.2: distinction between studies and reports; internal application to cohort/outcome linkage / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm data was developed internally. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid counting reports of the same dose arms, regulatory secondhand citations, reviews, or registrations as independent replication trials. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Link reports to trial families, endpoints, and analyses to distinguish same, different, and unknown relationships; leave the undetermined number of unique studies without a value.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The direct core evidence (evidence_core) consists only of ADVENT-2002. Other doses, abstracts/secondhand citations, and regulatory summaries from the same trial are not independent replication, and independent replication of the exact comparison was not verified in the current retained material.",
      "condition_status": "Unverified",
      "status_reason": "No material is available to verify independent replication of the exact comparison. Do not turn the 13 bibliographic records (citation) or reports from the same family into a replication count.",
      "missingness": "Independent results for the exact comparison and family-linkage material are needed.",
      "uncertainty": "Independent results for the exact comparison and family-linkage material are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Links between unique trials and reports, and independent results tables, for the exact comparison"
    },
    {
      "item_id": "N30",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Have funding, manufacturer-affiliated authors, and disclosed conflicts of interest in the direct trial been verified?",
      "needed": "Original funding information, author affiliations, product supply, speaking/stock/employment relationships, and COI disclosures",
      "role": "Supplementary; required for interpreting independence",
      "role_reason": "This is needed to avoid penalizing manufacturer support/author relationships again as trial-method bias, or automatically deleting the data.",
      "application_exception": "The presence of Kos support is not used to declare the figures invalid, nor as proof of independent funding or independent replication.",
      "criterion": "Funding, author affiliations, and disclosed relationships such as speaking/stock interests in the core trial are linked to their original locations.",
      "basis": "C10: Chamgap's own criteria for independence and attribution. The official methodological sections used in this pilot do not warrant all of these detailed items. Reason for adapting this to the comparative HbA1c harm question: This is needed to avoid penalizing manufacturer support/author relationships again as trial-method bias, or automatically deleting the data. No new clinical causality/grade judgment was made, and no official methodology was applied.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Distinguish and verify each source of funding, employment relationship, and disclosure, and examine the scope of claims of independence.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "ADVENT records Kos support, manufacturer-affiliated authors, and disclosed speaking/stock relationships. The original I0 is this historical classification and is not used as a new deduction under the criteria.",
      "condition_status": "Met",
      "status_reason": "The reported funding and author relationships in the direct trial are verified. This does not mean that independent replication has been verified or the actual magnitude of bias has been calculated.",
      "missingness": "Relationships beyond the disclosed scope and separate independent replication of the exact comparison have not been verified.",
      "uncertainty": "Relationships beyond the disclosed scope and separate independent replication of the exact comparison have not been verified. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Original funding information, author affiliations, product supply, speaking/stock/employment relationships, and COI disclosures"
    },
    {
      "item_id": "N31",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Can the products and versions in the official ER documents, and their differences from the historical trial, be verified?",
      "needed": "Products, versions, dates, description/warning sections in the DailyMed/FDA documents, and information linking them to the trial product",
      "role": "Supplementary; required for interpreting official safety information",
      "role_reason": "Needed to avoid automatically treating the 2026 generic label and the 2020 NIASPAN file as manufacturing details for the original trial, the latest documents, or estimates of the trial effect.",
      "application_exception": "The current official webpages/PDFs are not newly read, and their currency or jurisdiction-specific approvals are not rechecked.",
      "criterion": "The products, versions, and review scope of the official generic document available at the reference date and the historical NIASPAN document are distinguished.",
      "basis": "C05: M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / H08: M19 §19.1.2–19.2.4; internal application / E10: M19 §19.1.2–19.2.4; internal application. Reason for adaptation to the comparative HbA1c harm question: needed to avoid automatically treating the 2026 generic label and the 2020 NIASPAN file as manufacturing details for the original trial, the latest documents, or estimates of the trial effect. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare official documents by version, product, and date to distinguish exposure in the historical trial from the safety background.",
      "current_reports": [
        "S05",
        "S06"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "S05 is the AvPAK/AvKARE generic niacin ER label updated 2026-02-25 and revised 2/2026. S06 reuses the historical file of the 2020 NIASPAN PDF. Neither substitutes for evidence of the original trial's manufacturing batch, titration schedule, or HbA1c effect.",
      "condition_status": "Met",
      "status_reason": "The distinctions among products, versions, and roles in the retained bibliography and records are verified. This does not verify current web responses or currency as of 2026-10-05.",
      "missingness": "No check of current version updates or actual access responses was attempted in this review; detailed trial manufacturing information remains a separate gap.",
      "uncertainty": "No check of current version updates or actual access responses was attempted in this review; detailed trial manufacturing information remains a separate gap. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Products, versions, dates, description/warning sections in the DailyMed/FDA documents, and information linking them to the trial product"
    },
    {
      "item_id": "N32",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Can the collection of other harms, discontinuations, and exposure denominators in the same trial be verified?",
      "needed": "Trial AE definitions, collection procedures, group-specific exposure/events/discontinuations, duration data, and original locations of official warnings",
      "role": "Supplementary; required for interpreting overall safety",
      "role_reason": "Needed to avoid turning the failure to detect major liver or muscle events in a short trial, together with official warnings, into an event rate of 0 or overall safety.",
      "application_exception": "H04 is adapted only to data requirements for the frequency of separate events, such as liver/muscle events; it is not imposed as a mandatory incidence requirement for the continuous mean change in HbA1c.",
      "criterion": "Definitions, collection, group-specific person/event counts, durations, and discontinuations for other AEs in the same population under the same exposure are verified.",
      "basis": "H01: M19 §19.1.2–19.2.4; detailed distinctions are internally designed / H04: M19 §19.1.2–19.2.4; internal application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / E10: M19 §19.1.2–19.2.4; internal application. Reason for adaptation to the comparative HbA1c harm question: needed to avoid turning the failure to detect major liver or muscle events in a short trial, together with official warnings, into an event rate of 0 or overall safety. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Distinguish continuous HbA1c changes from separate AEs when comparing collection, exposure denominators, and person/event counts; do not fill unreported information with 0.",
      "current_reports": [
        "S01",
        "S05",
        "S06"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original safety wording states that failure to detect major liver or muscle events in the short trial does not guarantee long-term safety. Official ER warnings cover glucose, liver, urate/gout, flushing, and muscle harms with statin co-treatment. The current retained summary does not contain complete information on collection of other AEs or group-specific events/denominators in the selected trial.",
      "condition_status": "Partly verified",
      "status_reason": "The retained warnings and limited short-term observations are verified, but complete group-specific AE collection, denominators, and discontinuations have not been verified.",
      "missingness": "Systematic collection and group-specific exposure/event/discontinuation data for separate AEs are needed.",
      "uncertainty": "Systematic collection and group-specific exposure/event/discontinuation data for separate AEs are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Trial AE definitions, collection procedures, group-specific exposure/events/discontinuations, duration data, and original locations of official warnings"
    },
    {
      "item_id": "N33",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Can data on persistent HbA1c effects, long-term complications, and rare harms be verified?",
      "needed": "Exposure/follow-up data on HbA1c after discontinuation, long-term complications, rare events, and vulnerable groups",
      "role": "Supplementary; required for an extension to long-term/overall safety",
      "role_reason": "Needed to avoid establishing persistent effects, rare events, or risks in excluded vulnerable groups from short-term mean changes.",
      "application_exception": "Not every long-term study is unconditionally required to answer the narrow 16-week HbA1c claim, but gaps in extended claims remain explicit.",
      "criterion": "Appropriate follow-up data are available to verify persistent/long-term and rare harms for the selected population and product.",
      "basis": "H08: M19 §19.1.2–19.2.4; internal application / E08: M03 §3.2.1–3.2.4; details of dose, persistence, and effect modification are internally designed. Reason for adaptation to the comparative HbA1c harm question: needed to avoid establishing persistent effects, rare events, or risks in excluded vulnerable groups from short-term mean changes. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Distinguish long-term follow-up, repeated-measurement, and event-collection methods suited to the question; do not interpret short-term nondetection as long-term safety.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Long-term follow-up for the selected question has no value (null), and the original list of unverified matters (unknowns) states that the short-term design cannot determine the magnitude of persistent HbA1c effects, long-term complications, or rare harms.",
      "condition_status": "Unverified",
      "status_reason": "The core design did not investigate the long-term scope, and no verified data are available. This is neither a reason to delete the selected 16-week result nor a claim that no studies exist worldwide.",
      "missingness": "Direct data on long-term and rare harms for the selected exposure and population are needed.",
      "uncertainty": "Direct data on long-term and rare harms for the selected exposure and population are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Exposure/follow-up data on HbA1c after discontinuation, long-term complications, rare events, and vulnerable groups"
    },
    {
      "item_id": "N34",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Can the body text, results, and correspondence to ADVENT of the registry leads be verified?",
      "needed": "Official body text/history, results, and verified linkage data for DRKS00030865, NCT00108485, and NCT06378125",
      "role": "Supplementary; required for interpreting registrations/unpublished results",
      "role_reason": "Needed to avoid elevating registry completion/termination status, mirrors, or a JS shell to verified HbA1c results or replication of ADVENT.",
      "application_exception": "Do not assert that NCT06378125 and DRKS00030865 are the same registration without a verified cross-link. Do not display historical access failures as current failures.",
      "criterion": "The official body text, results, registry links, and correspondence to the selected ADVENT comparison are directly verified.",
      "basis": "C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; internal application to cohort/outcome linkage / C03: the data-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading, and the hyperlink conventions, are internally designed / C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm data is internally designed. Reason for adaptation to the comparative HbA1c harm question: needed to avoid elevating registry completion/termination status, mirrors, or a JS shell to verified HbA1c results or replication of ADVENT. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Compare each registration's population, release product, endpoints, results, and links to distinguish plans/status/mirror leads from clinical results.",
      "current_reports": [
        "S07",
        "S08",
        "S09",
        "S10"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "DRKS concerns a different intestinal-release product in healthy/prediabetic participants, and its HbA1c screening range is not a result. Historical access to the official NCT00108485 body text yielded a JS shell/API failure, with only a termination lead from a mirror available. The official NCT06378125 body text also yielded only a shell historically, and its cross-link to DRKS is unverified.",
      "condition_status": "Partly verified",
      "status_reason": "Some registry identities, different populations/products, and historical access limits are verified, but official results, reasons for termination, and correspondence among registrations have not been verified.",
      "missingness": "Materials directly verifying official body text/history, results, and registry links are needed.",
      "uncertainty": "Materials directly verifying official body text/history, results, and registry links are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Official body text/history, results, and verified linkage data for DRKS00030865, NCT00108485, and NCT06378125"
    },
    {
      "item_id": "N35",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Can the actual body text, scope, and family relationships of the review, protocol, and expression-of-concern notice be verified?",
      "needed": "The review's included trials/results tables, protocol body text, content/scope of the expression-of-concern notice, and document links",
      "role": "Supplementary; required for interpreting indirect evidence/editorial history",
      "role_reason": "Needed to avoid repurposing the existence of a review, an indexed protocol, or an expression-of-concern lead as confirmation of results or evidence of an ADVENT defect.",
      "application_exception": "Keep the spelling in the actual returned S13 link byte-for-byte. Do not add scope or ADVENT relevance without having read the original text of the expression-of-concern notice.",
      "criterion": "The actual content of the S11 included trials, S12 plans, and S13 notice, and their relationships to the corresponding documents/trials, are verified.",
      "basis": "C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; internal application to cohort/outcome linkage / C03: the data-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading, and the hyperlink conventions, are internally designed / C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application / H07: M04 §4.6.1–4.6.2; adaptation for harm data is internally designed. Reason for adaptation to the comparative HbA1c harm question: needed to avoid repurposing the existence of a review, an indexed protocol, or an expression-of-concern lead as confirmation of results or evidence of an ADVENT defect. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Distinguish results, plans, and editorial notices, attributing them only to the corresponding documents; do not count them as independent trials or extend them to unrelated trials.",
      "current_reports": [
        "S11",
        "S12",
        "S13"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "S11 was used only for discovery/cross-checking through bibliographic records and access-failure records; no pooled figures were adopted. S12 is an indexed protocol, not results. S13 is an indexed lead concerning that protocol; its body text and precise scope could not be read. This lead was not used as evidence against ADVENT.",
      "condition_status": "Partly verified",
      "status_reason": "Document types and linkage leads are available, but the actual details of the review content, protocol, and notice text have not been verified.",
      "missingness": "Actual body text, scope, included trials, and official document links are needed.",
      "uncertainty": "Actual body text, scope, included trials, and official document links are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "The review's included trials/results tables, protocol body text, content/scope of the expression-of-concern notice, and document links"
    },
    {
      "item_id": "N36",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Does this HbA1c comparison also answer questions about incident diabetes or cardiovascular/complication events?",
      "needed": "Definitions, denominators, follow-up, and between-group results for incident diabetes and cardiovascular/complication events in the selected comparison",
      "role": "Supplementary; required for an extension to clinical events",
      "role_reason": "Needed to avoid treating a mean difference in a surrogate as an increase in event incidence or long-term complications.",
      "application_exception": "Because the original question concerns HbA1c change itself, event trials are not imposed as an invariably mandatory condition for verifying that result.",
      "criterion": "Direct results are available to address the separate clinical-event question in the same population with the same product and comparison.",
      "basis": "C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed / E09: M03 §3.2.4; internally defined extension boundaries / H08: M19 §19.1.2–19.2.4; internal application / H09: Chamgap's own interpretive boundaries. The M19 principles are referenced; no official causality tool was applied. Reason for adaptation to the comparative HbA1c harm question: needed to avoid treating a mean difference in a surrogate as an increase in event incidence or long-term complications. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Review appropriate follow-up that measures and analyzes HbA1c and event endpoints separately, and do not estimate event effects from the surrogate alone.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "Fasting glucose, incident diabetes, lipids, FMD, and cardiovascular events are not substitute endpoints for the selected HbA1c success criterion. The current HbA1c increase does not establish differences in long-term complications or cardiovascular events.",
      "condition_status": "Unverified",
      "status_reason": "The selected material addresses the HbA1c comparison; this table has no material for verifying direct estimates of those clinical events.",
      "missingness": "If separate clinical events are asked about, direct event results, denominators, and follow-up are needed.",
      "uncertainty": "If separate clinical events are asked about, direct event results, denominators, and follow-up are needed. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Definitions, denominators, follow-up, and between-group results for incident diabetes and cardiovascular/complication events in the selected comparison"
    },
    {
      "item_id": "N37",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are current summary reading, each material's historical access/access date, and current external nonreading distinguished?",
      "needed": "Actual access, acquisition, and reading events for each material, original locations and dates, and hashes of the retained inputs",
      "role": "Required",
      "role_reason": "Needed to avoid treating historical full-text/abstract/access-failure records (full_text/abstract/access_failure) and original access dates as actions performed in this review.",
      "application_exception": "Do not describe current unattempted external access as access failure; use a historical access date only for a bibliographic record (citation) that actually has an access_date. Do not mark older separate files as having been read merely because they are referenced.",
      "criterion": "Local retained-summary reading, historical access/access dates for the 13 bibliographic records (citation), the original review date, and current unattempted/unread external access are recorded separately.",
      "basis": "C03: the data-collection/selection principles in M04 §4.5–4.6; the distinction between access and reading, and the hyperlink conventions, are internally designed / C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design. Reason for adaptation to the comparative HbA1c harm question: needed to avoid treating historical full-text/abstract/access-failure records (full_text/abstract/access_failure) and original access dates as actions performed in this review. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "Review actions for each material by event/date, and add an actual new external-reading event only when that reading is authorized.",
      "current_reports": [
        "S01",
        "S02",
        "S03",
        "S04",
        "S05",
        "S06",
        "S07",
        "S08",
        "S09",
        "S10",
        "S11",
        "S12",
        "S13"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "In this review, the complete KO/EN text, evidence, and bibliography in the current retained source summary were read. The 13 bibliographic records (citation) have access_date=2026-09-15 and different historical access levels. Access to all current external papers, labels, registrations, and mirrors was unattempted, and they were unread; the older separate original sources/trial_families files were not read either.",
      "condition_status": "Met",
      "status_reason": "The narrow condition of separately recording current local reading and the actual bibliographic records' (citation) historical access/access dates is verified. This does not mean current verification of external full texts.",
      "missingness": "Current comparison with external original materials was not performed, and access dates/levels are not retroactively reassigned.",
      "uncertainty": "Current comparison with external original materials was not performed, and access dates/levels are not retroactively reassigned. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Actual access, acquisition, and reading events for each material, original locations and dates, and hashes of the retained inputs"
    },
    {
      "item_id": "N38",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the original C46, 7 axes, document quality, and new condition statuses distinguished in what they describe?",
      "needed": "Original records of the assessment, axes, score meaning, document quality, and version",
      "role": "Required",
      "role_reason": "Needed to avoid reusing the original clinical-harm grade as a safety grade, risk rate, document-quality grade, or criterion-fulfillment rate.",
      "application_exception": "Preserve the original missing values, false values, axes, and score unchanged; do not change them to F or efficacy not_applicable merely because this is a harm claim.",
      "criterion": "The clinical-harm claim/increase designation (clinical_harm_claim/increase), C46 and B/S/R1/I0/EX/B2/CX, and the meaning of document self-review grade A are each linked to their original locations.",
      "basis": "C01: the question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / H09: Chamgap's own interpretive boundaries. The M19 principles are referenced; no official causality tool was applied. Reason for adaptation to the comparative HbA1c harm question: needed to avoid reusing the original clinical-harm grade as a safety grade, risk rate, document-quality grade, or criterion-fulfillment rate. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "If a correction becomes necessary, preserve the original event and before/after values, and review criterion revision and changes to the clinical assessment as separate tasks.",
      "current_reports": [
        "S01"
      ],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original clinical-harm claim is rated C, 46, with B/S/R1/I0/EX/B2/CX. This is the evidence tier for the increase claim, not risk magnitude, individual response, safety, or document quality. Document-quality grade A (document_quality) is a single-assistant self-review, not external independent certification.",
      "condition_status": "Met",
      "status_reason": "The original assessment and what each designation means are verified and preserved in the complete manuscript. This does not issue a new score, grade, risk rate, or declaration that the conditions are sufficient.",
      "missingness": "Gaps in clinical significance/precision remain under the other conditions and are not filled by the original score.",
      "uncertainty": "Gaps in clinical significance/precision remain under the other conditions and are not filled by the original score. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Original records of the assessment, axes, score meaning, document quality, and version"
    },
    {
      "item_id": "N39",
      "question_type": "Comparative harm: HbA1c increase",
      "question": "Are the current verification scope, evidence reference date, original server metadata, and update events stated?",
      "needed": "Evidence/review dates, actual retained search/selection records, versions, and update/correction events",
      "role": "Required",
      "role_reason": "Needed to avoid overstating conversion of retained materials as a current comprehensive search, completed public release, or absence of studies worldwide.",
      "application_exception": "Distinguish the historical dates in evidence_cutoff/verified_date from the current review date, and do not interpret the original first-publication date or the missing deployment timestamp (deployed_at, null) as a new deployment event.",
      "criterion": "The original reference date of 2026-09-15, the scope of review of current retained inputs, actual review dates, unverified information, update events, and nondeployment are distinguished.",
      "basis": "C09: M04 §4.5, §4.6.3; the limits of the current data conversion follow the user-defined scope and internal design / E06: M08 Table 8.2.a, M04 §4.6.3; internal application. Reason for adaptation to the comparative HbA1c harm question: needed to avoid overstating conversion of retained materials as a current comprehensive search, completed public release, or absence of studies worldwide. No new clinical causality/grade judgment or application of an official method was performed.",
      "condition_origin": "The internally developed criteria for this known development case, whose material has already been read, are frozen through a separate explicit instruction. This is not automatic copying, blinding, clinical preregistration or official methodological certification.",
      "proposed_research": "If authorized new materials become available, compare their identities, dates, original locations, and access levels, and review the linked conditions' observations and status reasons again.",
      "current_reports": [],
      "existence": "Limited to what has been verified within the currently retained manuscript, evidence and bibliography.",
      "acquired_read": "Summary reading: the material at the exact identified location in the retained source summary was read. The linked external material was not read in this review.",
      "observation": "The original reference date/verification date (verified_date) is 2026-09-15, and the current review date is 2026-10-05. The first-publication date denotes the original editorial issue date, while the deployment timestamp (deployed_at) has no value (null). Update triggers, including matching full texts, plans, corrections, and numerical/classification errors, are retained.",
      "condition_status": "Met",
      "status_reason": "Records of dates, scope, server-metadata meaning, and update conditions are distinguished from the actual original values. This does not mean that a current comprehensive literature search or public release was performed.",
      "missingness": "Older original search/selection files were not read, and checks for current external updates were not performed in this review.",
      "uncertainty": "Older original search/selection files were not read, and checks for current external updates were not performed in this review. No new clinical effects, risk rates, individual responses, or grades are calculated or judged.",
      "review_date": "2026-10-05",
      "reading_status": "Original source unread · Retained summary read",
      "additional_material": "Evidence/review dates, actual retained search/selection records, versions, and update/correction events"
    }
  ],
  "reports": [
    {
      "report_id": "S01",
      "title": "Grundy SM et al. ADVENT: Efficacy, Safety, and Tolerability of Once-Daily Niacin for the Treatment of Dyslipidemia Associated With Type 2 Diabetes. Arch Intern Med. 2002;162:1568–1576.",
      "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/212257",
      "report_type": "Publisher's original article in full-text HTML, with tables/figures (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": "ADVENT-2002",
      "independent_replication": "The actual study family recorded in the source's evidence/family_id field. The same trial's 1,000 mg arm and the presentation cited secondhand are not counted as independent replication.",
      "observed_result": "Record at the time of preservation: randomized, double-blind, parallel-group ADVENT. Overall, 148 participants were assigned/146 exposed; the selected-arm counts of 52/49 are not HbA1c analysis denominators. Including 4 weeks of titration, the total duration was 16 weeks, with a target of 1,500 mg/day during weeks 5–16. Changes were +0.29 versus −0.02 %p, with existing arithmetic of +0.31 %p and reported P=0.048; the formal change-contrast CI, variance, and endpoint n are unverified. The policy allowed diabetes-drug adjustment, continuation by existing statin users, and permitted/nonmandatory ASA; Kos funding and manufacturer-author/disclosure relationships are recorded. The same trial's 1,000 mg arm P=.16, the baseline 7.23%/7.28% conflict, and the secondhand citation of an unverified original presentation are preserved separately.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Publisher's original article in full-text HTML, with tables/figures (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: full-text HTML. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S01-M1",
          "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/212257"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/212257"
        }
      ]
    },
    {
      "report_id": "S02",
      "title": "Elam MB et al. Effect of Niacin on Lipid and Lipoprotein Levels and Glycemic Control in Patients With Diabetes and Peripheral Arterial Disease: The ADMIT Study. JAMA. 2000;284:1263–1270.",
      "url": "https://jamanetwork.com/journals/jama/fullarticle/193064",
      "report_type": "Publisher's original article in full-text HTML (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": "ADMIT",
      "independent_replication": "ADMIT is named in the original bibliographic citation (cite). It does not replicate the exact ADVENT comparison.",
      "observed_result": "Record at the time of preservation: ADMIT is a comparison involving IR Niacor, a different dose/run-in, factorial co-treatments, and a population/time-specific effect of interest. Within-group maintenance of HbA1c in the nicotinic-acid arm, while it fell in the placebo arm, differs from a null between-group effect. The abstract/table P discrepancy remains in the original record, but this retained summary contains no specific values.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Publisher's original article in full-text HTML (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: full-text HTML. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S02-M1",
          "url": "https://jamanetwork.com/journals/jama/fullarticle/193064"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://jamanetwork.com/journals/jama/fullarticle/193064"
        }
      ]
    },
    {
      "report_id": "S03",
      "title": "Garg A, Grundy SM. Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA. 1990;264:723–726.",
      "url": "https://pubmed.ncbi.nlm.nih.gov/2374275/",
      "report_type": "PubMed bibliographic record/abstract (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "The bibliography identifies a particular crossover study, but no structure linking unique study families is currently available. No new total of families or independent participants is issued.",
      "observed_result": "Record at the time of preservation: the abstract record describes a crossover study of 13 participants, 1 dose of 1.5 g taken three times daily, each period lasting 8 weeks, and a relative increase in glycosylated-hemoglobin. The exact release formulation and equivalence to the selected HbA1c assay are unverified. No independent-arm calculation was performed.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "PubMed bibliographic record/abstract (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: abstract. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S03-M1",
          "url": "https://pubmed.ncbi.nlm.nih.gov/2374275/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pubmed.ncbi.nlm.nih.gov/2374275/"
        }
      ]
    },
    {
      "report_id": "S04",
      "title": "Karim F et al. The therapeutic effectiveness of sitagliptin with niacin and chromium picolinate on glycosylated hemoglobin in type 2 diabetes mellitus patients. Biomed Res Ther. 2018;5(8):2610–2619.",
      "url": "https://bmrat.org/index.php/BMRAT/article/view/469",
      "report_type": "Publisher's original article in full-text HTML (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "The bibliography contains an individual clinical study, but its product/co-treatment differs from the selected ER comparison; no new total of unique families is issued.",
      "observed_result": "Record at the time of preservation: a study combining low-dose niacin 14 mg/day with sitagliptin reported improvement. The exact nicotinic acid/amide identity and release product are unverified, and this is not a comparison of prescription ER NIASPAN 1,500 mg/day. The chromium co-treatment arm in the methods is also not combined with the selected comparison.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Publisher's original article in full-text HTML (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: full-text HTML. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S04-M1",
          "url": "https://bmrat.org/index.php/BMRAT/article/view/469"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://bmrat.org/index.php/BMRAT/article/view/469"
        }
      ]
    },
    {
      "report_id": "S05",
      "title": "DailyMed: NIACIN extended-release tablets (AvPAK repackaged label; AvKARE adverse-event contact), updated 2026-02-25, revised 2/2026.",
      "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd60fe81-3d54-4a29-9502-601be89c575e",
      "report_type": "Full online text of the official DailyMed product label (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "An administrative/official label; no clinical trial family is assigned.",
      "observed_result": "Record at the time of preservation: the AvPAK/AvKARE generic niacin ER label updated 2026-02-25 and revised 2/2026. It provides background on glucose, liver, urate/gout, flushing, and muscle harms with statin co-treatment, as well as warnings about formulation substitution/titration. It is not used to impute the original NIASPAN manufacturing details, titration, or HbA1c effect, and its currency was not checked in this review.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Full online text of the official DailyMed product label (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: full-text HTML. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S05-M1",
          "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd60fe81-3d54-4a29-9502-601be89c575e"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=dd60fe81-3d54-4a29-9502-601be89c575e"
        }
      ]
    },
    {
      "report_id": "S06",
      "title": "FDA: NIASPAN extended-release niacin prescribing information, 2020.",
      "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf",
      "report_type": "FDA NIASPAN prescribing-information PDF and warning sections (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "An official document; no clinical trial family is assigned.",
      "observed_result": "Record at the time of preservation: the historical file of the 2020 NIASPAN prescribing information was reused, and a record states that the PDF warning pages were read. It was not displayed as a new, latest label; S05 serves the role of the safety-document check at the reference date. Product descriptions and liver/glucose/muscle/urate warnings are distinguished from the trial effect.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "FDA NIASPAN prescribing-information PDF and warning sections (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: full-text document PDF. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S06-M1",
          "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020381s054lbl.pdf"
        }
      ]
    },
    {
      "report_id": "S07",
      "title": "DRKS00030865: controlled ileocolonic-release nicotinic acid safety/pharmacokinetic study.",
      "url": "https://drks.de/search/en/trial/DRKS00030865",
      "report_type": "Official DRKS online registry record (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "The DRKS00030865 registry identifier is retained, but it is not counted as a new trial result or replication of ADVENT.",
      "observed_result": "Record at the time of preservation: a safety/pharmacokinetic study of a different ileocolonic-release nicotinic acid product in healthy/prediabetic participants. The HbA1c screening range is not an efficacy result, and completed status does not prove that HbA1c results are publicly available.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Official DRKS online registry record (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: registry body text. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S07-M1",
          "url": "https://drks.de/search/en/trial/DRKS00030865"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://drks.de/search/en/trial/DRKS00030865"
        }
      ]
    },
    {
      "report_id": "S08",
      "title": "ClinicalTrials.gov record NCT00108485.",
      "url": "https://clinicaltrials.gov/study/NCT00108485",
      "report_type": "Official ClinicalTrials.gov registration page/JS shell (historical failure to access body text)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "It has the same registration number as S09. This does not verify official results, the reason for termination, correspondence to ADVENT, or a clinical study family.",
      "observed_result": "Record at the time of preservation: the official page was a JS shell at the time, and the API search also failed. Because the original body text/results could not be verified, endpoints, termination reasons, and results were not inferred. No access attempt was made in this review.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Official ClinicalTrials.gov registration page/JS shell (historical failure to access body text)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical failure to access body text. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S08-M1",
          "url": "https://clinicaltrials.gov/study/NCT00108485"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://clinicaltrials.gov/study/NCT00108485"
        }
      ]
    },
    {
      "report_id": "S09",
      "title": "Study of the Use of Niaspan for Treatment of Dyslipidemia in Diabetic Nephropathy — registry mirror lead.",
      "url": "https://ctv.veeva.com/study/study-of-the-use-of-niaspan-for-treatment-of-dyslipidemia-in-diabetic-nephropathy",
      "report_type": "Veeva secondary (2nd-source) registry mirror web record (historically read)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "It has the same registry identifier as S08, but the mirror lead is not counted as an independent trial or clinical result.",
      "observed_result": "Record at the time of preservation: a lead for a terminated study under NCT00108485 and a link to the official record were found. Mirror information was not elevated to verified clinical results or used for scoring, and the official body text was inaccessible.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Veeva secondary (2nd-source) registry mirror web record (historically read)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical secondary (2nd-source) registry mirror. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S09-M1",
          "url": "https://ctv.veeva.com/study/study-of-the-use-of-niaspan-for-treatment-of-dyslipidemia-in-diabetic-nephropathy"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://ctv.veeva.com/study/study-of-the-use-of-niaspan-for-treatment-of-dyslipidemia-in-diabetic-nephropathy"
        }
      ]
    },
    {
      "report_id": "S10",
      "title": "ClinicalTrials.gov NCT06378125: nicotinic-acid intestinal-release study lead.",
      "url": "https://clinicaltrials.gov/study/NCT06378125",
      "report_type": "Official ClinicalTrials.gov registration page/JS shell (historical failure to access body text)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "Whether NCT06378125 and DRKS00030865 are the same registration remains unverified without a verified cross-link.",
      "observed_result": "Record at the time of preservation: only a JS shell was verified on the official NCT06378125 page at the time. No verified link establishing that it was the same registration as DRKS00030865 was obtained, and neither registration was counted as replication of the core comparison.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Official ClinicalTrials.gov registration page/JS shell (historical failure to access body text)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical failure to access body text. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S10-M1",
          "url": "https://clinicaltrials.gov/study/NCT06378125"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://clinicaltrials.gov/study/NCT06378125"
        }
      ]
    },
    {
      "report_id": "S11",
      "title": "Xiang et al. Effectiveness of niacin supplementation for patients with type 2 diabetes: A meta-analysis of randomized controlled trials. Medicine. 2020;99:e21235.",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7373507/",
      "report_type": "Reference to a PMC review page and indexed bibliography (historical failure to access the full text)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "The review is not a new independent human trial. The families and overlap of its included trials are currently unverified.",
      "observed_result": "Record at the time of preservation: only the bibliography of the 2020 review was verified; access to the PMC full text encountered a challenge, and the publisher returned HTTP 402. No pooled figures were adopted, and the review was not counted as an independent trial.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Reference to a PMC review page and indexed bibliography (historical failure to access the full text)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical bibliographic information/access failure. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S11-M1",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7373507/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7373507/"
        }
      ]
    },
    {
      "report_id": "S12",
      "title": "The efficacy of niacin supplementation in type 2 diabetes patients: Study protocol of a randomized controlled trial.",
      "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9282106/",
      "report_type": "Reference to a PMC protocol page and indexed bibliography (historical failure to access the full text)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "A planning document, not human trial results or confirmation of membership in the ADVENT family.",
      "observed_result": "Record at the time of preservation: the plan's title and identifiers were verified in an index, but full-text access failed. A protocol is not results. There is a link lead to the S13 expression-of-concern notice, but its details were not fully verified, and it was not used as evidence of an ADVENT-related defect.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Reference to a PMC protocol page and indexed bibliography (historical failure to access the full text)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical bibliographic information/access failure. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S12-M1",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9282106/"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9282106/"
        }
      ]
    },
    {
      "report_id": "S13",
      "title": "Expression of Concern: Study protocols (indexed notice lead, Medicine 2025).",
      "url": "https://journals.lww.com/md-journal/fulltext/2025/11070/expmression_of_concern__study_protocols.160.aspx",
      "report_type": "Publisher's expression-of-concern notice link and indexed bibliography (historical failure to access body text)",
      "existence": "A reference in the retained bibliography and historical records; the current external response has not been checked.",
      "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials were not read in this review.",
      "study_family": null,
      "independent_replication": "An editorial notice is not an independent human trial. A lead unrelated to ADVENT is not attributed to the ADVENT harm result.",
      "observed_result": "Record at the time of preservation: an indexed lead to a 2025 expression-of-concern notice was linked to S12, but the publisher's body text and the precise scope of the notice could not be read. The expmression spelling in the actual returned URL was preserved exactly; the lead was not used as evidence to discredit the independent ADVENT report.",
      "result_level": "This information is recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.",
      "source_evidence_date": "2026-09-15",
      "materials": [
        {
          "material_type": "Publisher's expression-of-concern notice link and indexed bibliography (historical failure to access body text)",
          "public_status": "Currently unverified",
          "access_status": "Not attempted in this review",
          "acquired": false,
          "actually_read": "Unread",
          "as_of": "2026-11-01",
          "qualification": "Historical access date for the material: 2026-09-15; recorded level: historical bibliographic information/access failure. Only the retained summary was read in this review; external access was not attempted, and the material was neither acquired nor read.",
          "material_id": "S13-M1",
          "url": "https://journals.lww.com/md-journal/fulltext/2025/11070/expmression_of_concern__study_protocols.160.aspx"
        }
      ],
      "links": [
        {
          "label": "Source",
          "url": "https://journals.lww.com/md-journal/fulltext/2025/11070/expmression_of_concern__study_protocols.160.aspx"
        }
      ]
    }
  ],
  "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 criteria, and reasons for changes, and distinguish variations in the intervention.",
      "review_level": "Reused the original HTML bytes/SHA copies and historical principles from 1585's 5 retained methods. This was not new full-text methods reading or official assessment/certification."
    },
    {
      "id": "M04",
      "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04",
      "section": "§4.5, §4.6.1–4.6.3, MECIR C42",
      "official_principle": "Distinguish studies from reports and link them; do not omit a study solely because results were not reported.",
      "review_level": "Reused the original HTML bytes/SHA copies and historical principles from 1585's 5 retained methods. This was not new full-text methods reading or official assessment/certification."
    },
    {
      "id": "M08",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08",
      "section": "§8.1–8.2.3, Table 8.2.a",
      "official_principle": "Fix the outcome and effect of interest when reviewing randomization, departures, missing data, measurement, and selective reporting.",
      "review_level": "Reused the original HTML bytes/SHA copies and historical principles from 1585's 5 retained methods. This was not new full-text methods reading or official assessment/certification."
    },
    {
      "id": "M15",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15",
      "section": "§15.2.4, §15.3.1–15.3.3",
      "official_principle": "Distinguish effect estimates, intervals, importance, and application. Sample size alone does not determine precision.",
      "review_level": "Reused the original HTML bytes/SHA copies and historical principles from 1585's 5 retained methods. This was not new full-text methods reading or official assessment/certification."
    },
    {
      "id": "M19",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19",
      "section": "§19.1.2, §19.2.1–19.2.4",
      "official_principle": "Questions about harms may require designs, populations, and follow-up different from those for efficacy. Case reports do not establish incidence.",
      "review_level": "Reused the original HTML bytes/SHA copies and historical principles from 1585's 5 retained methods. This was not new full-text methods reading or official assessment/certification."
    }
  ],
  "status_dictionary": {
    "Met": "The specific narrow identity, definition, attribution of verified numbers, policy, or boundary of the actual record is verified. This does not certify clinical harm, a formal interval, or overall safety.",
    "Partly verified": "Some actual information is verified in the original material, but the product, denominator, analysis, or full estimate for the question remains incomplete.",
    "Unverified": "Cannot be established within the current retained scope. This does not mean an effect of 0, absence of studies worldwide, or current access failure.",
    "Conflicting information": "Original reports of the same fact do not agree. Successful recording of the conflict is distinguished from verification that the clinical data are consistent.",
    "Not reported": "Limited to nonreporting within the explicitly stated material accessed at the time. This is not a claim of absence throughout a full text left unread in this review.",
    "Not applicable": "Used when there is a specific reason why the applicability conditions of the current question are not met. Not a substitute for unverified or unread status.",
    "Inaccessible": "Historical failures are distinguished from actual current access failures. This status is not assigned to unattempted external access in this review.",
    "Review incomplete": "Limited to the current nonperformance of comparisons against external original material; distinguished from the local retained-summary review that was actually completed."
  },
  "study_overlap": {
    "state": "ADVENT-2002: the 1,000 mg arm and the conference presentation cited secondhand are not counted as separate independent replication. ADMIT: an indirect comparison with a different IR formulation, dose, run-in, population, and time-specific effect of interest. NCT00108485: official shell/secondary (2nd-source) mirror leads for the same registry identifier. Clinical results, correspondence to ADVENT, and the number of unique studies are unverified. The direct exact comparison belongs to the single ADVENT-2002 family. The 13 reports do not mean 13 independent trials; the total numbers of unique trials and participants are unverified.",
    "unique_trial_count": null,
    "unique_participant_count": null,
    "reason": "ADVENT-2002: the 1,000 mg arm and the conference presentation cited secondhand are not counted as separate independent replication. ADMIT: an indirect comparison with a different IR formulation, dose, run-in, population, and time-specific effect of interest. NCT00108485: official shell/secondary (2nd-source) mirror leads for the same registry identifier. Clinical results, correspondence to ADVENT, and the number of unique studies are unverified. The direct exact comparison belongs to the single ADVENT-2002 family. The 13 reports do not mean 13 independent trials; the total numbers of unique trials and participants are unverified."
  },
  "history": [
    {
      "date": "2026-11-01",
      "kind": "Separation of the public view and materials",
      "view_version": "1.0",
      "change": "The public view and materials were prepared from the existing 39 items. No new clinical search, change in verification status, or scoring was performed."
    }
  ],
  "language": "en",
  "translation_date": "2026-11-01"
}