{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Folic acid × Reduction of BDI-II depression severity as an antidepressant adjunct",
  "criteria_version": "NGM-v3109-FOLATED-BDI-II-AUC-1.0",
  "criteria_date": "2026-10-05",
  "condition_origin": "Chamgap application criteria",
  "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": "Reuse of case 1585 methodological principles/versions and byte-for-byte copies of 5 HTML files; no new reading of complete methods texts or application of an official tool in this review"
    },
    {
      "id": "M04",
      "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04",
      "section": "§4.5, §4.6.1–4.6.3, MECIR C42",
      "official_principle": "Distinguish and link studies and reports, and do not omit a study solely because its outcomes are not reported.",
      "review_level": "Reuse of case 1585 methodological principles/versions and byte-for-byte copies of 5 HTML files; no new reading of complete methods texts or application of an official tool in this review"
    },
    {
      "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": "Hold the outcome and effect of interest fixed, then assess randomization, deviations, missing data, measurement and selective reporting.",
      "review_level": "Reuse of case 1585 methodological principles/versions and byte-for-byte copies of 5 HTML files; no new reading of complete methods texts or application of an official tool in this review"
    },
    {
      "id": "M15",
      "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08",
      "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15",
      "section": "§15.2.4, §15.3.1–15.3.3",
      "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.",
      "review_level": "Reuse of case 1585 methodological principles/versions and byte-for-byte copies of 5 HTML files; no new reading of complete methods texts or application of an official tool in this review"
    },
    {
      "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 efficacy questions. Case reports do not establish incidence.",
      "review_level": "Reuse of case 1585 methodological principles/versions and byte-for-byte copies of 5 HTML files; no new reading of complete methods texts or application of an official tool in this review"
    }
  ],
  "status_dictionary": {
    "Partly verified": "Some preserved information is available, but gaps remain in manufacturing, exposure, plans, denominators, harms and original sources",
    "Unverified": "Necessary information or conditions cannot be established within this review's scope",
    "Review incomplete": "Original-source comparisons or searches were not performed within the permitted scope",
    "Not reported": "A scope-limited status indicating that the item was not stated in the particular material or section read",
    "Inaccessible": "Used only for material for which access was actually attempted and failed. Not assigned to clinical materials in this review.",
    "Insufficient eligible evidence": "Used only when, after reviewing relevant studies within a defined scope, evidence is insufficient to answer the condition. Not applied universally in this review.",
    "Not applicable": "An extension beyond the selected AUC comparison is not applicable; this does not substitute for actual unverified information",
    "Conflicting information": "Used when comparison reveals information that is difficult to reconcile for the same question, time point and analysis. Not assigned solely because review estimates differ.",
    "Met": "The stated preservation, boundary, distinction or linkage condition is verified; this does not mean new clinical efficacy verification, full-text reading or safety certification",
    "Conflicting printed values": "The conflict between printed values in the original record is preserved; no new calculation or correction"
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Distinct claim",
      "question": "Which folic acid adjunct regimen and BDI-II outcome are being asked about?",
      "needed": "Current original claim, actual population, 5 mg/day for 12 weeks, common antidepressant policy, placebo, and the 0–25-week time-weighted mean BDI-II",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid extending the conclusion to all folic acid and all depression.",
      "application_exception": "L-methylfolate, combination products, biomarkers and the single 25-week endpoint are not framed as the same question.",
      "criterion": "Link the original claim to the boundaries of the actual regimen, comparison and time-weighted endpoint.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Review direct results within these boundaries separately from materials addressing other questions."
    },
    {
      "item_id": "N02",
      "question_type": "Ingredient and product",
      "question": "Are the actual folic acid product and unverified manufacturing details distinguished?",
      "needed": "Active ingredient, 5 mg tablet, overencapsulation, filler, Bilcare supply, and documentation of salt/manufacturer/lot/purity",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid equating the supplier with the manufacturing source or with other folate products.",
      "application_exception": "The authorized Flamingo product does not establish the identity of the FolATED product.",
      "criterion": "Record the reported active ingredient and overencapsulation separately from unverified manufacturing details.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare trial product, batch and ingredient records with the original medication section."
    },
    {
      "item_id": "N03",
      "question_type": "Route and nominal dose",
      "question": "Is 5 mg as 1 daily dose the same as actual total exposure?",
      "needed": "Oral route, nominal amount for 1 dose and dosing frequency, dosing records and total exposure",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning the trial dose into an individual recommendation or a claim of actual complete adherence.",
      "application_exception": "Do not calculate new cumulative doses, conversions or recommended doses.",
      "criterion": "Distinguish the planned oral 5 mg as 1 daily dose from unverified actual exposure.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Link arm-specific dosing, missed doses and adherence records to the effect of interest."
    },
    {
      "item_id": "N04",
      "question_type": "Treatment and observation",
      "question": "Are 12 weeks of treatment distinguished from 25 weeks of observation?",
      "needed": "End of trial treatment, observation measured from randomization, and visit times",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning 25 weeks of observation into 25 weeks of treatment or a lasting long-term effect.",
      "application_exception": "Do not impose all long-term follow-up as a requirement for this narrow question.",
      "criterion": "Show 12 weeks of treatment separately from observation through 25 weeks.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "If persistence after treatment discontinuation is the question, review direct estimates and exposure at that time."
    },
    {
      "item_id": "N05",
      "question_type": "Placebo and background treatment",
      "question": "What were the matching placebo and common antidepressant policy?",
      "needed": "Lactose placebo, visual matching for blinding, optimization/usual-care policy, and individual drug names/doses",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid describing a shared policy as identical drugs and doses for all participants.",
      "application_exception": "Do not automatically exclude comparative results because concomitant treatment was used.",
      "criterion": "Distinguish the actual added-ingredient contrast from the common policy and unverified individual exposure.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Link arm-specific antidepressants and medication changes to the selected BDI-II analysis."
    },
    {
      "item_id": "N06",
      "question_type": "Changes and concurrent exposure",
      "question": "Were medication changes, psychotherapy and dietary/supplement exposure verified?",
      "needed": "Arm-specific antidepressant changes, rescue treatment, psychotherapy, dietary/fortified-food/supplement exposure and their handling",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid describing permitted changes as absent or attributing the result solely to folic acid.",
      "application_exception": "Do not impose a new condition that all changes must be identical.",
      "criterion": "Separate the permitted clinical context from unverified actual treatment and exposure histories.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare arm-specific changes and concurrent-exposure records with how the effect of assignment was handled."
    },
    {
      "item_id": "N07",
      "question_type": "Diagnosis and baseline status",
      "question": "Which adult MDD population and screening criteria were used?",
      "needed": "Clinician diagnosis under ICD10, moderate/severe depression, BDI-II screening/randomization criteria, and new/existing antidepressant use",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid recasting the population as entirely treatment-resistant depression or as general low mood.",
      "application_exception": "Do not generalize trial screening cutpoints into diagnostic criteria for all clinical care.",
      "criterion": "Preserve BDI-II screening ≥19 and randomization ≥17, clinician diagnosis and the actual population boundaries.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Link original inclusion/exclusion criteria, recruitment and baseline status to the actual denominators."
    },
    {
      "item_id": "N08",
      "question_type": "Nutritional status",
      "question": "Does deficiency screening establish normal nutritional status in everyone?",
      "needed": "Folate/B12 deficiency screening, baseline values/units and subgroups with low values",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning a screening policy into a claim that every participant had normal status.",
      "application_exception": "Do not repurpose results from a small low-value subgroup as the overall primary effect or an effect in confirmed deficiency.",
      "criterion": "Preserve screening records, small low-value subgroups and unverified units separately.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare baseline tests/units and eligibility with the prospective plan for stratified analyses."
    },
    {
      "item_id": "N09",
      "question_type": "Pregnancy and lactation",
      "question": "Is restricting the page to nonlactating adults the same as verifying actual lactation status?",
      "needed": "Exclusion of pregnancy/planned pregnancy, lactation inclusion/exclusion criteria and actual status",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning a page restriction into a record that lactating participants were actually excluded from the trial.",
      "application_exception": "Do not turn unverified lactation status into confirmed harm, efficacy or exclusion during lactation.",
      "criterion": "Separate exclusion of pregnancy/planned pregnancy from unverified lactation status.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare actual eligibility criteria, lactation status and evidence for special populations separately."
    },
    {
      "item_id": "N10",
      "question_type": "BDI-II measurement",
      "question": "Are the subjective scale's direction and collection distinguished from blinding?",
      "needed": "BDI-II total score, lower-is-better direction, collection at visits, matching placebo/blinding, and limitations in implementation",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid asserting absence of all measurement bias solely from the scale name or double blinding.",
      "application_exception": "Do not treat a subjective scale as an automatic failure or recast it as a biomarker.",
      "criterion": "Explain the patient-reported depression total score, reported blinding and the extent of implementation not cross-checked.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Link scale collection and blinding implementation at each visit to the selected analysis."
    },
    {
      "item_id": "N11",
      "question_type": "AUC definition and units",
      "question": "How should the time-weighted mean be interpreted?",
      "needed": "Area across baseline and weeks 4/12/25, divided by the actual observation period; mean expressed in BDI-II points",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid recasting it as point-weeks, within-group change or a single endpoint.",
      "application_exception": "Do not perform new AUC calculations or conversions in this review.",
      "criterion": "Link the final plan's time-weighted AUC average, units and adjusted between-group estimand.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare definitions of the estimand and units in the original SAP and results tables."
    },
    {
      "item_id": "N12",
      "question_type": "Plan changes",
      "question": "Were the initial 25-week endpoint and the final AUC the same from the outset?",
      "needed": "Original protocol, erratum, final SAP, unblinding/amendment approval dates and registration history",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid concealing the endpoint change and unverified details.",
      "application_exception": "Do not turn an unavailable plan into confirmed selective reporting or a claim of an identical prospective plan from the outset.",
      "criterion": "Show separately the initial single time point, final AUC, reportedly pre-unblinding SAP and unverified approval date.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare protocol, erratum and SAP versions, registration changes and approval timing."
    },
    {
      "item_id": "N13",
      "question_type": "Design and allocation",
      "question": "To what extent are the actual comparative design and allocation process verified?",
      "needed": "Multicenter individually randomized parallel groups, matching placebo, allocation/concealment and baseline balance",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid extending the design label into complete verification of concealment and baseline balance.",
      "application_exception": "Do not turn unverified details into a nonrandomized classification or automatic failure.",
      "criterion": "Distinguish the recorded actual design from details not cross-checked in this review.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M08 §8.1–8.2.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Link original randomization/concealment information and baseline tables to the selected outcome."
    },
    {
      "item_id": "N14",
      "question_type": "Allocation and analysis denominators",
      "question": "What do the denominators of 475 and 440 represent?",
      "needed": "Valid allocation 237/238, total 475; 35 with no follow-up BDI-II; mITT 223/217, total 440",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid substituting the allocation denominator for analysis or completion denominators.",
      "application_exception": "Do not create dropout rates, new denominators or new calculations in this review.",
      "criterion": "Preserve allocation, reasons for exclusion and primary-analysis denominators together with their arms.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare the original flowchart, analysis definitions and loss to follow-up by arm."
    },
    {
      "item_id": "N15",
      "question_type": "mITT and missing data",
      "question": "Does regression imputation include the 35 excluded participants?",
      "needed": "Assigned groups retained; inclusion requires at least 1 follow-up; imputation within the 440; sensitivity analysis of all randomized participants",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid calling imputation full ITT or removing the B1 defect.",
      "application_exception": "Do not infer that imputation within the included group brought excluded participants into the primary analysis.",
      "criterion": "Separate the inclusion criteria for modified ITT from the scope of imputation and exclusions.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original missing-data reasons, imputation and sensitivity methods with the effect of interest."
    },
    {
      "item_id": "N16",
      "question_type": "Sensitivity analyses and completion denominators",
      "question": "Are alternative analyses of the same trial counted as new replications?",
      "needed": "Complete-case, repeated mixed-model and reweighted-allocation analyses; denominators for completing visits and for complete BDI data",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning analysis counts into trial counts or collapsing different completion denominators into one.",
      "application_exception": "Do not infer exact completion denominators absent from the current summary.",
      "criterion": "Preserve sensitivity analyses within the same family and the differences in denominators.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original Tables 18–20 and participant flow with each analysis denominator and result."
    },
    {
      "item_id": "N17",
      "question_type": "Primary effect and direction",
      "question": "What exact comparison and interval does +1.09 points refer to?",
      "needed": "Table 13 adjusted folic acid minus placebo, 0–25-week AUC average, CI/P, 223/217 and lower-is-better direction",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid presenting a positive value as improvement or recasting it as a within-group or endpoint difference.",
      "application_exception": "Do not calculate new effects, CIs, P values or standardized estimates.",
      "criterion": "Preserve +1.09, CI −0.48 to 2.66 and P=0.173 together with the original estimand.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original Table 13, narrative text, analysis definitions and printed values."
    },
    {
      "item_id": "N18",
      "question_type": "SE conflict",
      "question": "Do the printed SE and CI/P in Table 13 agree?",
      "needed": "Printed SE 0.86, CI/P, and records of numerical conflicts in tables and narrative text",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid deleting problematic printed values or silently replacing them with recalculated values.",
      "application_exception": "Preserve the historical conflict record; do not conduct a new normal-approximation check or generate new values.",
      "criterion": "Preserve both the printed values and the explanation of the conflict.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M15 §15.3.1–15.3.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "During an authorized correction, compare the original table, analysis output and errata, and retain before-and-after values."
    },
    {
      "item_id": "N19",
      "question_type": "Unadjusted sign conflict",
      "question": "Were +0.06 and −0.06 overwritten with the same sign?",
      "needed": "Unadjusted AUC difference in Tables 12/18, the sign printed in each table, and distinction from the adjusted primary effect",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid erasing the sign conflict or transferring it to the adjusted primary effect.",
      "application_exception": "Differences between analyses are not automatically treated as conflicts, but the actual conflict recorded here is preserved.",
      "criterion": "Retain the original conflict between +0.06 in Table 12 and −0.06 in Table 18 unchanged.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original tables/directions, errata and analysis outputs as a separate correction event."
    },
    {
      "item_id": "N20",
      "question_type": "Interpreting nonsignificance",
      "question": "Does failure to demonstrate benefit mean an effect of 0, equivalence or ineffectiveness in all MDD?",
      "needed": "Direction of the primary effect, CI, fixed question and original meaning of E0",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning nonsignificance into established absence of effect or equivalence.",
      "application_exception": "Do not remove positive results for other doses, populations or scales.",
      "criterion": "Distinguish failure to demonstrate improvement in this narrow comparison from the range allowed by the interval.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M15 §15.3.1–15.3.3; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Review direct results for the same estimand and relevant clinical thresholds alongside additional evidence."
    },
    {
      "item_id": "N21",
      "question_type": "MCID and precision",
      "question": "Is the initial 3-point power target the MCID for AUC?",
      "needed": "Reported CI, a validated between-group threshold for clinical importance of the AUC average, and the initial 3-point target at 25 weeks",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid using a power target as an MCID or as evidence excluding clinically important benefit.",
      "application_exception": "Do not create a universal minimum sample size, duration or study count, or a new MCID.",
      "criterion": "Separate the unverified applicable AUC MCID from the role of the initial design target.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M15 §15.3.1–15.3.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare a justified threshold for the same endpoint and estimand with the CI."
    },
    {
      "item_id": "N22",
      "question_type": "Single 25-week result",
      "question": "Are endpoint means, adjusted endpoint differences and the primary AUC separated?",
      "needed": "Adjusted 25-week difference +1.27/CI/P, arm-specific unadjusted means and SDs, and distinct estimands",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid combining different results into one primary effect.",
      "application_exception": "Do not calculate new endpoint differences, standardized estimates or change scores.",
      "criterion": "Preserve the three types of values, the 25-week time point and units separately.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare Table 14 and Appendix 10/Table 42 with the original analysis definitions."
    },
    {
      "item_id": "N23",
      "question_type": "Reports and trial families",
      "question": "Are FolATED reports and appendices counted as independent trials?",
      "needed": "FOLATED links among the report, Methods/Results, protocol/erratum, SAP, registration and appendices",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid inflating independent replication or participant counts from the number of documents.",
      "application_exception": "Keep verified document identities separate from the unverified complete registration history.",
      "criterion": "Preserve the 11 linked reports S01/02/03/04/06/07/08/09/10/12/18 as one FOLATED family.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Verify the unique recruitment/allocation identity and distinctions from other families at the original locations."
    },
    {
      "item_id": "N24",
      "question_type": "Coppen positive result",
      "question": "Why is the positive female-subgroup HDRS-17 result not counted as direct replication?",
      "needed": "127 participants, 500 µg/day, 10 weeks, fluoxetine 20 mg, female-subgroup HDRS17, and subgroup denominators/plans",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid deleting favorable adjacent results or transferring them to FolATED's overall AUC.",
      "application_exception": "Do not infer the exact female denominator or prospective interaction testing.",
      "criterion": "Preserve 6.8 (SD 4.1) versus 11.7 (SD 6.7), P<0.001, and the different population stratum, dose, scale and duration.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare the abstract's scope with subgroup plans/denominators and the direct comparison in the original full text."
    },
    {
      "item_id": "N25",
      "question_type": "Another positive BDI-II result",
      "question": "What role does the uncorrected author proof for 2.5 mg over 8 weeks have?",
      "needed": "Sepehrmanesh 45/45, citalopram 20 mg, 2.5 mg/day for 8 weeks, BDI-II, and version/registration",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid calling it replication of the 5 mg, 25-week AUC solely because it uses the same scale name.",
      "application_exception": "Do not upgrade an uncorrected author proof to complete verification of the final published version.",
      "criterion": "Preserve the positive result of 13.31 (SD 6.57) versus 19.11 (SD 8.59), P<0.001, together with version limitations.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare the final publication version, registration history, denominators and plans with the different exposures and estimands."
    },
    {
      "item_id": "N26",
      "question_type": "Candidate with results not obtained",
      "question": "Was Resler metadata promoted to verified results?",
      "needed": "PMID18716414/DOI, the scope of access failure, and actual dose/denominators/effect",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid promoting a literature candidate to verified efficacy or a replication count.",
      "application_exception": "Access failure does not mean absence of a study or an effect of 0.",
      "criterion": "Separate candidate identity from unverified full-text results.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "If separately obtaining the source is authorized, link the original results, design, exposure and denominators."
    },
    {
      "item_id": "N27",
      "question_type": "Reviews and pediatric exclusion",
      "question": "Were reviews and trials in people younger than 18 combined with direct adult results?",
      "needed": "Discovery role of reviews S16/19, population boundary for pediatric S17, and original families",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid counting reviews and material outside the adult population as independent adult replications.",
      "application_exception": "Preserve the roles of reviews and excluded material without deleting them.",
      "criterion": "Distinguish evidence mapping and exclusion from the adult population from unverified direct results.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "If needed, separately compare underlying trial identities, adult-population boundaries and actual results."
    },
    {
      "item_id": "N28",
      "question_type": "Unfavorable SF-12 result",
      "question": "Was the secondary SF-12 result merged into BDI-II worsening or confirmed harm?",
      "needed": "SF12 mental-health AUC −1.97/CI/P, favoring placebo, and nominal secondary comparison",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid concealing an unfavorable result or repurposing it as a different endpoint.",
      "application_exception": "Do not turn nominal secondary significance into established clinical harm.",
      "criterion": "Preserve −1.97, CI −3.49 to −0.44, P=0.012 and the endpoint's role and multiplicity context.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.4; internally defined boundaries for extending the claim; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original Table 13, the plan, multiplicity and clinical meaning for that scale."
    },
    {
      "item_id": "N29",
      "question_type": "Subgroups and biochemistry",
      "question": "Do small subgroups, response/remission or blood results replace the primary effect?",
      "needed": "Plans, denominators and individual results for low-folate/genotype/sex subgroups, response/remission and biochemistry",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid using favorable selected results as the overall BDI-II primary effect.",
      "application_exception": "Do not fill in new quantitative effects or interactions absent from the current summary.",
      "criterion": "Preserve the existence and roles of other results and the boundaries of the primary effect.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Separately compare prospective subgroup/interaction plans, denominators, multiplicity and original results."
    },
    {
      "item_id": "N30",
      "question_type": "Funding and conflicts of interest",
      "question": "Does public funding mean there are no competing interests?",
      "needed": "NIHR HTA04/35/08, COBALZ advisory/shareholder roles, Bilcare supply and funding for adjacent studies",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid extending public funding into a guarantee of no conflicts or bias.",
      "application_exception": "Do not automatically exclude results because a competing interest exists.",
      "criterion": "Preserve verified public funding together with disclosed author and supplier relationships.",
      "basis": "Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare the original funding/COI/supply information and the scope of adjacent-study disclosures."
    },
    {
      "item_id": "N31",
      "question_type": "Adverse events and counts",
      "question": "Are 33/45 and 6/14 counts of events or people?",
      "needed": "25-week AE 33/45, SAE 6/14, possible drug reactions 4/3, and unique-person denominators/collection",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning event counts into unique patient counts, incidence or NNH.",
      "application_exception": "Do not calculate new harm rates, comparative risks or NNH.",
      "criterion": "Distinguish reported event counts and observation duration from unverified person denominators.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.2 questions about harms by study design; details of temporal relationships are internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare event definitions and collection, exposure, unique people and missingness in original Tables 15–17."
    },
    {
      "item_id": "N32",
      "question_type": "0 events within a reaction category",
      "question": "Are 0 serious/unexpected reactions being read as 0 events overall?",
      "needed": "Scope of 0 serious or unexpected reactions among the 4/3 possible drug reactions",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid extending 0 in one subcategory to all AE/SAE or to long-term absence of risk.",
      "application_exception": "Do not turn failure to verify a significant difference into equivalence or an assurance of safety.",
      "criterion": "State both the category to which 0 refers and the overall event counts.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original reaction classifications, seriousness/expectedness and collection scope."
    },
    {
      "item_id": "N33",
      "question_type": "MINI risk classification",
      "question": "Do 25/223 and 28/217 represent suicide attempts or deaths?",
      "needed": "25-week MINI high-risk category, imputed analysis with 223/217, and actual suicidal-behavior/death events",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning a scale classification into counts of actual behavior or deaths.",
      "application_exception": "Do not fill unverified behavior or death counts with 0.",
      "criterion": "Separate risk-category counts of 25/223 and 28/217 from unverified separately counted events.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations for each study design are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Compare original MINI definitions, imputation, collection and actual event records with their respective denominators."
    },
    {
      "item_id": "N34",
      "question_type": "Official safety materials",
      "question": "What is the scope of documents on B12 masking and interactions?",
      "needed": "Masking of hematological signs of B12 deficiency, neurological problems, antiepileptics/methotrexate, and partial NIH material/SmPC",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid using general context from official documents as FolATED incidence or independent events.",
      "application_exception": "Citing an official document again does not constitute a new independent event or evidence of authorization for depression.",
      "criterion": "Record general safety context, the scope of material access, and boundaries between other products and trial data.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed differentiation is internally designed; M19 §19.2 questions about harms by study design; details of temporal relationships are internally designed; M19 §19.2.2–19.2.4 considerations for study design; detailed recording of confounding is internally designed; M04 §4.6.1–4.6.2; adaptations for harms data are internally designed; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Separately compare original safety documents, case/study families, exposure, timing and alternative explanations."
    },
    {
      "item_id": "N35",
      "question_type": "Long-term use and vulnerable populations",
      "question": "Does 25-week observation answer every long-term or special-population safety question?",
      "needed": "Direct exposure and events for high-dose/long-term use, pregnancy/lactation/children, hepatic/renal disease and cancer history",
      "role": "Required for extended harm questions",
      "role_reason": "Needed to avoid expanding narrow observation into assurances for all vulnerable populations or rare harms.",
      "application_exception": "Do not impose studies in all special populations as requirements for this narrow efficacy question.",
      "criterion": "Distinguish trial scope from each unverified extended harm question.",
      "basis": "M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundaries. M19 principles are referenced; no official causality assessment tool was applied",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "Separately design or review material suited to the relevant exposure, population and long-term/rare events."
    },
    {
      "item_id": "N36",
      "question_type": "Reading and dates",
      "question": "Is reading summaries distinguished from past reading of external sources?",
      "needed": "Exact locations/values/SHA of current stored summaries, access levels of 19 bibliographic entries, report-specific access dates and evidence cutoff date",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid upgrading a summary link to current full-text verification or using the review date as an access date.",
      "application_exception": "Do not label external access not attempted as access failure.",
      "criterion": "Link the local summaries actually read in this review separately from past access levels and unread external sources.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "When original materials are actually obtained, separately preserve material types, dates, locations read and original bytes."
    },
    {
      "item_id": "N37",
      "question_type": "Searches, registration and corrections",
      "question": "Does the prior search scope represent a current exhaustive search or retraction check?",
      "needed": "2026-09-15 search scope, partial/failed registration access, protocol correction, and the scope of checking retractions/new evidence",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning 0 new searches in this review into 0 studies, proof of absence, or a claim that no recent corrections exist.",
      "application_exception": "Do not merge a protocol erratum and a correction to original results into the same event.",
      "criterion": "Link existing search/correction records to the scope of work currently not performed and information remaining unverified.",
      "basis": "M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "During a separately authorized search or correction, preserve complete original texts, events, before-and-after values and versions."
    },
    {
      "item_id": "N38",
      "question_type": "Original grade and certification",
      "question": "Are D30 and B/P/R1/I2/E0/B1/C0 being presented as a new verdict?",
      "needed": "Original grade/score/axes, 1 strength, document quality A, self-review and clinical certification=false",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid turning table-criterion counts, colors or structural checks into a new efficacy score or clinical certification.",
      "application_exception": "External content QA is inspection of the current table conversion; it is not retroactively treated as independent review of the original clinical assessment.",
      "criterion": "Preserve the original D30/Caution, 7 axes, meaning of E0, document quality and review level unchanged.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design; Chamgap's own criteria for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items; M15 §15.3.1–15.3.3; internal application",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "If a correction is separately authorized, record the original evidence, verdict, reasons and before-and-after values as an event."
    },
    {
      "item_id": "N39",
      "question_type": "Boundaries for extending efficacy claims",
      "question": "Are optimal dose, biomarkers, remission and mortality combined into the same answer?",
      "needed": "The selected AUC question and direct questions about other doses/durations, L-methylfolate, B-vitamin combinations and clinical events",
      "role": "Required for extended efficacy questions",
      "role_reason": "Needed to avoid requiring all extension studies for the selected numerical outcome or extrapolating automatically.",
      "application_exception": "Do not use inapplicability of an extension as a substitute for actual unverified product, plan or MCID information.",
      "criterion": "Keep efficacy questions outside the selected question within separate boundaries.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptations for each question are internally designed; M03 §3.2.1–3.2.4; details on dose, duration and effect modification are internally designed; M03 §3.2.4; internally defined boundaries for extending the claim",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "If an extension is asked about, separately compare direct dose, follow-up and event data."
    },
    {
      "item_id": "N40",
      "question_type": "ID, publication and updates",
      "question": "Do historical deployment flags mean that this table has now been publicly published?",
      "needed": "Original 3109/assigned code/URL, server_deployed true/write false, dates, update policy and before-and-after original text",
      "role": "Required for the selected FolATED BDI-II comparison",
      "role_reason": "Needed to avoid presenting historical identity/deployment wording as completed public publication of the current local sheet.",
      "application_exception": "Do not arbitrarily correct differences in original metadata wording or extend deployment authorization.",
      "criterion": "Preserve original identity and wording, and distinguish local unpublished status and versions of criteria, observations and events.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.5–4.6 principles for collecting/selecting material; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses is internally designed; M04 §4.5, §4.6.3; limits on the present conversion of material reflect the user-defined scope and internal design",
      "condition_origin": "Known development criteria designed after actually reading the current 3109 source materials; not blinded, clinically preregistered or independently clinically certified",
      "proposed_research": "During an authorized update, retain complete originals, original values/contrary results, reasons for changes and versions."
    }
  ]
}