{
  "schema_version": "chamgap-public-criteria-1.0",
  "title": "Vitamin C (single-ingredient oral L-ascorbic acid) × Change in symptomatic stone recurrence in adults with prior calcium-oxalate stones",
  "criteria_version": "NGM-v3116-ORAL-C-SYMPTOMATIC-CAOX-RECURRENCE-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": "Historical reuse of the actual retained HTML copy and SHA from 1585 and the methodological principles from that time. This is not new reading of the methods full text, a formal application, or clinical certification in this work."
    },
    {
      "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": "Historical reuse of the actual retained HTML copy and SHA from 1585 and the methodological principles from that time. This is not new reading of the methods full text, a formal application, or clinical certification in this work."
    },
    {
      "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": "Historical reuse of the actual retained HTML copy and SHA from 1585 and the methodological principles from that time. This is not new reading of the methods full text, a formal application, or clinical certification in this work."
    },
    {
      "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": "Historical reuse of the actual retained HTML copy and SHA from 1585 and the methodological principles from that time. This is not new reading of the methods full text, a formal application, or clinical certification in this work."
    },
    {
      "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": "Historical reuse of the actual retained HTML copy and SHA from 1585 and the methodological principles from that time. This is not new reading of the methods full text, a formal application, or clinical certification in this work."
    }
  ],
  "status_dictionary": {
    "Met": "Verification of the relevant retained/question condition; not confirmation of a clinical effect",
    "Unverified": "Required direct material/values are not verified within the current scope",
    "Conflicting information": "Used when an actual conflict concerning the same material/value is linked",
    "Not met": "Used when the required condition does not match what was actually verified",
    "Not applicable": "Used when a condition is not imposed on the particular question",
    "Not read": "The external original material was not actually read in this work",
    "Access failed": "Used only when an actual access failure occurred in this work",
    "Partly verified": "Some verified content coexists with gaps in applicability or data"
  },
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Claim and boundaries of the independent question",
      "question": "Which adults, oral intervention and recurrent-stone event does this table address?",
      "needed": "The original /ko/effect and question specifications for population, ingredient, route, event, comparison and time",
      "role": "Required",
      "role_reason": "Needed to avoid converting stone risk factors or first incident stones into symptomatic recurrence in patients with a history of stones.",
      "application_exception": "The question definition alone does not establish a recurrence direction, dose or duration as a verified effect or prescription. The absence of a subclaims field is also preserved.",
      "criterion": "Link the single question of comparative change in symptomatic new stones in adults with a calcium-oxalate stone history receiving pure single-ingredient oral L-ascorbic acid to the excluded questions.",
      "basis": "Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; 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 adaptation for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation for each question is internally designed; M03 §3.2.4; internally defined limits on extrapolation",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Subsequent research should define symptomatic new calcium-oxalate stone recurrence as the main outcome and report imaging-only events, residual-stone growth and first incident stones separately."
    },
    {
      "item_id": "N02",
      "question_type": "Reference date and reading scope",
      "question": "What materials were actually read this time, and what are the historical access records?",
      "needed": "The retained summary's evidence cutoff, access records for each source, locations actually read in the current work and file SHA",
      "role": "Required",
      "role_reason": "Needed to avoid presenting past full-text/abstract access on 2026-09-16 as full-text reading performed this time.",
      "application_exception": "Current external access not attempted is not labeled as access failure. Past failures stated in the manuscript are retained only as historical records.",
      "criterion": "Separate reading of the current local stored summary from not having read clinical original texts, registrations and official documents this time, material by material.",
      "basis": "Principles for data collection/selection in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data transformation follow the user-defined scope and internal design",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "For subsequent material verification, separately record material type, version, access attempts, sections actually read and the SHA of acquired files, and cross-check them against historical summaries."
    },
    {
      "item_id": "N03",
      "question_type": "Reports and study families",
      "question": "Have the 17 reports been kept from being double-counted as independent recurrence trials?",
      "needed": "A mapping of each report's source_id to study family, cohort, endpoint and repeat citations",
      "role": "Required",
      "role_reason": "Needed to avoid counting publisher, PubMed and PMC versions, reviews and related metabolic reports as separate trials.",
      "application_exception": "Retain the possible S04/S17 overlap as a single conservative cluster, without confirming that they involve the same participants.",
      "criterion": "Link the roles of the 10 retained families and S11–S16 documents without creating an unverified unique-participant total.",
      "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2; adaptation for harms material is internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Create an overlap ledger that cross-checks original participant recruitment, registration, study locations and timing to verify Chai/Massey overlap and cohort reuse."
    },
    {
      "item_id": "N04",
      "question_type": "Ingredient, formulation and route",
      "question": "Has the question's pure oral L-ascorbic acid been distinguished from other forms?",
      "needed": "Product ingredient list, L isomer, salts, single/combined ingredients and actual administration route",
      "role": "Required",
      "role_reason": "Needed to avoid importing foods, salts, combination products or injections as recurrence effects of the pure oral preparation.",
      "application_exception": "Harms from injections may be retained as a separate context, but are not transferred as effects or incidence for the single-ingredient oral preparation.",
      "criterion": "Identify the question's formulation boundary and distinguish it from verification of actual study-product eligibility.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Subsequent comparisons should verify batch-specific ingredients, salts/isomers, added ingredients and administration routes, distinguishing them from food/injection exposures."
    },
    {
      "item_id": "N05",
      "question_type": "Actual product identity",
      "question": "Have the product, source and single-ingredient status of a directly eligible recurrence study been verified?",
      "needed": "Product, batch, manufacturing source, purity, ingredient list and original methods for a direct recurrence comparison",
      "role": "Required",
      "role_reason": "Because the name ascorbic acid alone cannot establish eligibility as a pure L single ingredient.",
      "application_exception": "Preserve nominal ingredients in indirect reports unchanged, without using them to fill gaps in the eligible product.",
      "criterion": "Use original data to verify whether the actual product in the selected direct comparison matches the question's formulation.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Design research linking product analysis or verifiable ingredient lists to the actual comparison groups and administration records."
    },
    {
      "item_id": "N06",
      "question_type": "Population and stone history",
      "question": "Is this direct evidence about adults with a confirmed history of calcium-oxalate stones?",
      "needed": "Age, prior stone diagnosis/composition, recurrence history, baseline status and inclusion/exclusion table",
      "role": "Required",
      "role_reason": "Needed to avoid recasting general-population, cystine-stone or mixed-stone groups as adults with a calcium-oxalate stone history.",
      "application_exception": "The question's editorial boundary of adulthood at age 18 is not transferred as the actual minimum age in each study.",
      "criterion": "Verify the actual population's age, prior stone composition and diagnosis, and whether it matches the question's population.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M19 §19.1.2–19.2.4; detailed distinctions are internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Analyze prior stone composition and verify history before recruitment, reporting data for adults with a calcium-oxalate stone history separately from other compositions."
    },
    {
      "item_id": "N07",
      "question_type": "S01 selection and composition denominators",
      "question": "How are S01's 43 identified, 24 included and 17 composition-verified participants distinguished?",
      "needed": "Patient selection flow, age, sex, stone-composition testing table and reasons for exclusion",
      "role": "Required",
      "role_reason": "Needed to avoid using the total identified population, included group and composition-tested group as the same recurrence-analysis denominator.",
      "application_exception": "A calcium-oxalate cell of 0 in the follow-up composition table is not interpreted as 0 calcium-oxalate recurrences among all 24 participants.",
      "criterion": "Link S01's recruited, included, composition-verified and event groups separately within the original reporting scope.",
      "basis": "M03 §3.2.1; detailed population criteria are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by design are internally designed; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Subsequent research should disclose participant-level flow and missing tests from recruitment through composition testing and event adjudication."
    },
    {
      "item_id": "N08",
      "question_type": "S01 composite events",
      "question": "What outcome and follow-up period do the 8/24 events in S01 represent?",
      "needed": "Event tables by new-stone and residual-stone-growth component, symptom status, composition, and median or fixed follow-up information",
      "role": "Required",
      "role_reason": "This is needed to avoid presenting a mixed composite event as a symptomatic calcium-oxalate recurrence rate or a causal effect.",
      "application_exception": "Preserve the fact that urinary pH was the original study's main endpoint and stone events were a secondary endpoint. Do not turn pH or oxalate P values into recurrence P values.",
      "criterion": "Attribute 8/24, 33.3%, and the median follow-up of 22.6 months only to the original composite outcome.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M03 §3.2.4; internally defined limits on extension; M19 §19.1.2–19.2.4; detailed distinctions were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Comparative studies are needed that adjudicate new stones, growth of existing stones, and symptomatic events separately, and distinguish prespecified fixed-time outcomes from time to first recurrence."
    },
    {
      "item_id": "N09",
      "question_type": "S01 nominal exposure",
      "question": "Is the dose in S01 a regimen from a directly eligible trial?",
      "needed": "Nominal daily dose, product, dose per administration/frequency, meal timing, actual intake, and administration records",
      "role": "Required",
      "role_reason": "This is needed to avoid using a dose from an indirect report involving mixed stone types as an established regimen for the target population.",
      "application_exception": "Do not turn the median of 1000 mg/day and range of 500–2000 mg/day into an individual recommendation or a direct dose comparison.",
      "criterion": "Distinguish the verified nominal dose in S01 from the unverified product, frequency, and duration of intake.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details concerning dose, duration, and effect modification were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Obtain the product and daily and per-administration dosing records, adherence, and changes in exposure by group to compare nominal dose with actual exposure."
    },
    {
      "item_id": "N10",
      "question_type": "Direct comparator",
      "question": "Has a recurrence comparator involving no addition, placebo, or the same care been verified?",
      "needed": "Comparators, care, concomitant interventions, event counts, and correspondence with the exposure group in the same population",
      "role": "Required",
      "role_reason": "This is needed to avoid mistaking events observed in an exposure group for a between-group increase or decrease in risk.",
      "application_exception": "The metabolic placebo condition in S02 and the healthy participants in S03 do not replace a comparator for the recurrence question.",
      "criterion": "Link the actual comparator for the target event and the effect of interest to the original result.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare an added single-ingredient oral preparation with no addition/placebo on top of the same usual care, and record events by group together with differences in care."
    },
    {
      "item_id": "N11",
      "question_type": "Duration and principal follow-up time",
      "question": "Have the treatment duration and principal follow-up time for comparing recurrence been verified?",
      "needed": "Actual treatment start/end, discontinuation, follow-up/censoring, and prespecified principal follow-up time",
      "role": "Required",
      "role_reason": "This is needed to avoid turning median follow-up or 3/6-day metabolic exposure into a fixed clinical recurrence period.",
      "application_exception": "Do not create a common minimum duration. Do not round a median of 22.6 months into a fixed 24-month result.",
      "criterion": "Distinguish the treatment duration, fixed time point, and time-to-event analysis of a directly eligible comparison within the verified scope.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M03 §3.2.1–3.2.4; details concerning dose, duration, and effect modification were internally designed; design-specific harms questions in M19 §19.2; details of temporal relationships were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Prespecify a defensible principal time point considering event accumulation and discontinuation/censoring, and report treatment duration separately from follow-up duration."
    },
    {
      "item_id": "N12",
      "question_type": "Event definition and measurement",
      "question": "Can symptomatic new stones be distinguished from imaging-only events and residual-stone growth?",
      "needed": "Symptoms, imaging/diagnosis, stone composition, adjudicators, definitions of new and residual stones, and event collection procedures",
      "role": "Required",
      "role_reason": "This is needed to avoid combining different clinical and imaging events as the same recurrence outcome.",
      "application_exception": "Emergency care, procedures, and time to first recurrence are separate outcomes and are not all added together as a single event.",
      "criterion": "Link the definition, diagnosis, and adjudication of the target event and its distinction from other events to the direct result.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4; internally defined limits on extension; M19 §19.1.2–19.2.4; detailed distinctions were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Apply event adjudication with group information masked where possible and standardized procedures for verifying symptoms, imaging, and composition."
    },
    {
      "item_id": "N13",
      "question_type": "Direct effect and uncertainty",
      "question": "Have an effect estimate, CI, and P value for an eligible recurrence comparison been verified?",
      "needed": "Events/denominators and time by group, original risk ratio/risk difference/HR, CI, P value, and analysis definition",
      "role": "Required",
      "role_reason": "This is needed to avoid filling in a recurrence comparison effect with indirect proportions, metabolic-measure P values, or first-stone HRs.",
      "application_exception": "Preserve unverified values as empty values and do not make new calculations from rounded proportions or other outcomes.",
      "criterion": "Attribute the estimate, direction, measure, and interval of a directly eligible comparison to its event and time point.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Report relative and absolute effects and intervals for prespecified symptomatic recurrence using the same analysis population and a fixed time point or a time-to-event model."
    },
    {
      "item_id": "N14",
      "question_type": "Design, allocation, and confounding",
      "question": "Have an actual design and allocation that support a causal comparison of recurrence been verified?",
      "needed": "Direct comparison methods, allocation/concealment, baseline risk, observational-study confounding/selection, and models",
      "role": "Required",
      "role_reason": "This is needed to avoid claiming that a causal comparison of the target recurrence has been resolved merely because a related study is labeled an RCT.",
      "application_exception": "Retain metabolic crossover trials and observational reports while distinguishing them from designs addressing the target event.",
      "criterion": "Verify actual design, allocation, and confounding information for the target outcome, and distinguish the axes that must remain unverified.",
      "basis": "M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Prespecify a randomized comparison on top of the same usual care or an appropriate comparative design that explicitly addresses confounding and selection pathways."
    },
    {
      "item_id": "N15",
      "question_type": "Concomitant interventions, adherence, and contribution",
      "question": "Can common treatments, deviations from medication use, and concomitant interventions be separated from vitamin C's contribution?",
      "needed": "Fluid intake/diet, medications/procedures, rescue treatment, adherence, exposure changes, and their handling in analysis by group",
      "role": "Required",
      "role_reason": "This is needed to avoid attributing the results of concomitant treatments or exposure changes to the contribution of a single-ingredient oral preparation.",
      "application_exception": "Do not assume that there were no concurrent changes. The acute course with antibiotics/stenting in S09 is not an effect on recurrence prevention.",
      "criterion": "Distinguish actual concomitant interventions and deviations from exposure needed to define the effect of interest from the unverified scope.",
      "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Collect fluid intake, diet, concurrent medications/procedures, rescue treatments, and actual medication use/discontinuation by group, and analyze them in accordance with the prespecified effect of interest."
    },
    {
      "item_id": "N16",
      "question_type": "Denominators and events/people",
      "question": "Have recurrence events, people, exposure time, and analysis denominators been verified?",
      "needed": "Numbers allocated/exposed, completing follow-up, and analyzed; recurrent events/people with events; follow-up time; and censoring tables",
      "role": "Required",
      "role_reason": "This is needed to avoid confusing data in which a person experiences multiple events with proportions of people or incidence rates.",
      "application_exception": "Do not turn the 8/24 count of people with composite events into an eligible incidence rate or a denominator specific to calcium-oxalate recurrence.",
      "criterion": "Verify the analysis denominator, event unit, time, and interval of the direct result together.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M19 §19.1.2–19.2.4; internal application; M08 §8.2.2, M15 §15.3.1; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Separate people with events from recurrent events using participant IDs and a time axis, and disclose denominators and censoring for first-recurrence and recurrent-event analyses."
    },
    {
      "item_id": "N17",
      "question_type": "Missing data, selection, and censoring",
      "question": "Who was included, lost to follow-up, or censored, and how was the target outcome handled?",
      "needed": "Participant flow, missing outcomes, censoring, reasons for exclusion, and analysis/sensitivity-analysis plans",
      "role": "Required",
      "role_reason": "This is needed to avoid extending observations limited to the included exposure group to the entire recruited population or presenting them as results without missing data.",
      "application_exception": "Do not present unverified full texts or flow diagrams as evidence of no missing data or a definite magnitude of bias.",
      "criterion": "Distinguish actual participant flow from missingness/censoring of the target recurrence, and explicitly identify unverified handling.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Disclose losses to follow-up, missing event ascertainment, and reasons for censoring by group, and perform prespecified sensitivity analyses for missing data."
    },
    {
      "item_id": "N18",
      "question_type": "Differences in detection and adjudication",
      "question": "Were symptom assessment, imaging, and event adjudication conducted under the same conditions across groups?",
      "needed": "Examination schedules, symptom collection, imaging/composition testing, masking/adjudicators, and detection/reporting pathways",
      "role": "Required",
      "role_reason": "This is needed to avoid mistaking imaging findings in a more frequently examined group for an actual difference in symptomatic recurrence.",
      "application_exception": "Do not mark masking or equivalent detection as met merely because imaging data are objective.",
      "criterion": "Explain the collection, adjudication, and detection conditions for the direct target event and what remains unverified.",
      "basis": "M08 Table 8.2.a, M03 §3.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions were internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Apply the same follow-up/symptom contacts and prespecified event adjudication procedures across groups, and disclose examination frequency together with missing adjudication."
    },
    {
      "item_id": "N19",
      "question_type": "Precision and important differences",
      "question": "Can the reported interval and a clinically important difference in recurrence be interpreted?",
      "needed": "Direct recurrence effect, CI, events/denominators, and a justified criterion for an important difference",
      "role": "Required",
      "role_reason": "This is needed to avoid declaring recurrence evidence sufficient on the basis of publication count, sample size, or statistical significance alone.",
      "application_exception": "Do not create uniform minimum participant counts, minimum durations, or numerical thresholds for important differences. Do not calculate an absent CI from indirect reports.",
      "criterion": "Record the relationship between the interval for the selected event and the importance criterion, or the reason this remains unverified.",
      "basis": "M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Prespecify a difference in recurrence justified from clinical and patient perspectives, and report the effect interval and basis for precision for that event and follow-up."
    },
    {
      "item_id": "N20",
      "question_type": "Planning, registration, and reporting",
      "question": "Have prespecified recurrence endpoints, the principal time point, and analyses been compared with actual reporting?",
      "needed": "Registration, protocol, analysis plan, amendment history, and actual results tables for the direct trial",
      "role": "Required",
      "role_reason": "This is needed to avoid turning unavailable planning materials into a definite conclusion of nonregistration or selective reporting.",
      "application_exception": "Do not use a registration shell or a mirror lead as an actually eligible recurrence protocol.",
      "criterion": "Explain prespecification status and the parts not compared at each relevant location.",
      "basis": "M08 Table 8.2.a, M04 §4.6.3; internal application; M04 §4.5, §4.6.3; limits on the current data transformation reflect the user-defined scope and internal design",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Disclose the recurrence event definition, principal time point, comparator, analysis/interval, missing-data handling, and reasons for changes in advance, and compare them with the final results."
    },
    {
      "item_id": "N21",
      "question_type": "Short-term crossover and urinary outcomes",
      "question": "Which population, exposure, and comparison does the crossover metabolic result in S02 describe?",
      "needed": "Original S02 methods/results tables, population, duration, sample, crossover contrast, and urinary oxalate units",
      "role": "Supplementary; required for attributing indirect results",
      "role_reason": "This is needed to retain controlled short-term urinary results while distinguishing them from clinical recurrence outcomes.",
      "application_exception": "Do not turn urinary oxalate or the authors' description of a 33% increase into a probability of symptomatic recurrence.",
      "criterion": "Distinguish the actual roles of the 12 calcium-oxalate stone formers and 12 nonformers, 6-day periods, 1 g twice daily, 41.0/30.5 mg, and P.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.4; internally defined limits on extension",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "For metabolic crossover trials, disclose the original paired comparison, diet, and sequence; assess the clinical recurrence question through separate long-term event follow-up and comparisons."
    },
    {
      "item_id": "N22",
      "question_type": "Crossover sequence and paired uncertainty",
      "question": "Have the sequence, washout period, paired variance, and carryover effects in S02 been verified?",
      "needed": "S02 full text, allocation sequence, washout period, results by period, paired variance, and carryover/deviation analyses",
      "role": "Supplementary; required for interpreting crossover results",
      "role_reason": "This is needed to avoid calculating a parallel-group CI or a clinical event difference from crossover sample sizes and means alone.",
      "application_exception": "Do not fill unavailable methods with assumptions of no washout, definite carryover, or paired variance of 0.",
      "criterion": "State the boundary between the currently verified crossover design and the unverified sequence and paired uncertainty.",
      "basis": "M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Report participant-level period contrasts, period/sequence, carryover effects, and missingness from the original crossover data according to the prespecified plan, and disclose the necessary paired uncertainty."
    },
    {
      "item_id": "N23",
      "question_type": "Short-term before–after and healthy-participant comparison",
      "question": "What was compared in the before–after metabolic study S03?",
      "needed": "Original S03 methods/results, stone composition, exposure/testing by group, the role of healthy participants, and paired data",
      "role": "Supplementary; required for interpreting indirect data",
      "role_reason": "This is needed to avoid using healthy participants as recurrence comparators for people with prior stones or extending before–after changes into an effect of adding treatment.",
      "application_exception": "The description 'calcium stone formers' alone does not establish that everyone had a verified history of calcium-oxalate recurrence.",
      "criterion": "Preserve the role of the 3-day urinary measures for the groups of 23/24 among the 47 stone formers and for the 20 healthy participants, and separate them from the target event.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M03 §3.2.4; internally defined limits on extension",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Disclose paired comparisons, composition, and diet/exposure for short-term metabolic data; study recurrence in adults with verified prior stones using a separate comparator receiving the same care."
    },
    {
      "item_id": "N24",
      "question_type": "Bibliography and unresolved duplication",
      "question": "Have detailed results and participant overlap between S04 and S17 been verified?",
      "needed": "Full texts of both original reports, populations/recruitment, study IDs, participant overlap, and original results tables",
      "role": "Supplementary; required for interpreting duplication and existence",
      "role_reason": "This is needed to avoid counting the existence of metadata as acquisition of actual results or as two independent replications.",
      "application_exception": "A conservative single cluster is not a conclusion proving that the participants were the same. Leave unverified DOI/PMID information as it is.",
      "criterion": "Separate the titles/bibliographic information actually read from unverified methods, numbers, and duplication, and do not sum participants or trials.",
      "basis": "The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; data collection/selection principles in M04 §4.5–4.6; the separation of access and reading and the hyperlink contract were internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare recruitment periods, institutions, participants, and designs in the two original reports to verify whether they belong to the same family, and update only the scope for which results have actually been acquired."
    },
    {
      "item_id": "N25",
      "question_type": "Cystine recurrence and passage",
      "question": "How are the cystine course and spontaneous passage in S05 distinguished?",
      "needed": "S05 German full text, composition, ages, event definitions, exposure/time, comparators, and complete participant flow",
      "role": "Supplementary; required for interpreting unfavorable results and scope",
      "role_reason": "This is needed to retain contrary or unfavorable human results without mixing other stone compositions and events into the target recurrence.",
      "application_exception": "Do not add the 2 people with spontaneous passage to new-recurrence events or turn the 17 participants into a denominator for adult calcium-oxalate recurrence.",
      "criterion": "Preserve the respective roles of the 17 participants, 5 g/day, 5 people with unchanged recurrence, 2 people with spontaneous passage, and the limitations concerning pediatric indexing and duration.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "For cystine data, separately verify composition, age, recurrence versus passage, concomitant interventions/exposure, and follow-up in the original report, and analyze them separately from calcium-oxalate studies."
    },
    {
      "item_id": "N26",
      "question_type": "Favorable small report",
      "question": "To what extent has the favorable report of 4 people in S06 been verified?",
      "needed": "S06 full text, exact ages, exposure/product, events, denominators, comparison, follow-up, and concomitant interventions",
      "role": "Supplementary; required for retaining positive evidence",
      "role_reason": "This is needed to retain a favorable report without filling in unavailable conditions as evidence of target efficacy.",
      "application_exception": "Do not treat the description 'young patients with cystinuria' as equivalent to adults with prior calcium-oxalate stones.",
      "criterion": "Record both the existence of the favorable description involving 4 people and the unverified detailed eligibility and original numerical values.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses was internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify the identity, ages, composition, exposure, events/time, and comparator in the original small report, then attribute the result only to the scope of the corresponding question."
    },
    {
      "item_id": "N27",
      "question_type": "Urinary cystine and publication timing",
      "question": "Have the favorable urinary result in S07 and the original report date been distinguished?",
      "needed": "Original 1982 S07 report, clinical events/follow-up, composition, exposure, and publication/digital identity",
      "role": "Supplementary; required for interpreting indirect evidence and identity",
      "role_reason": "This is needed to avoid transferring improvements in urinary measures to improved recurrence or counting a digital date as a new study.",
      "application_exception": "Do not turn the description of urinary cystine and sediment in 31 people into a controlled clinical recurrence result.",
      "criterion": "Distinguish the original 1982 report from the digitization date, and distinguish the scope of the 31 participants, 5 g/day, and urinary outcomes.",
      "basis": "The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses was internally designed; M03 §3.2.4; internally defined limits on extension",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare the original publication identity with the actual patient data, and verify cystine urinary measures and clinical recurrence as separate outcomes and follow-up."
    },
    {
      "item_id": "N28",
      "question_type": "First occurrence and observational association",
      "question": "How does the first-stone cohort result in S08 differ from the recurrence question?",
      "needed": "Original S08 population/history, sex, exposure, covariates, events/time, HR/CI, and records of cohort reuse",
      "role": "Supplementary; required for interpreting observational and indirect results",
      "role_reason": "This is needed to avoid transferring a first-occurrence association in a large observational sample to a causal effect on recurrence in people with prior stones.",
      "application_exception": "Do not create a combined effect or denominator that erases sex differences, unverified formulations, or cohort reuse.",
      "criterion": "Preserve the actual roles of the 156,735 women, 40,536 men, 6,245 events, median 11.3–11.7 years, and the supplement contrast in men.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations were internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify exclusions based on stone history, exposure/formulation, covariates, events/follow-up by sex, and reuse of the original cohorts; study the causal recurrence question through a separate comparison in a population with prior stones."
    },
    {
      "item_id": "N29",
      "question_type": "Acute dissolution and concomitant-treatment case report",
      "question": "To which interventions and event is the acute dissolution course in S09 attributable?",
      "needed": "Original S09 case report, exact title/bibliographic information, stone composition, concurrent/subsequent exposure, and acute/recurrence follow-up",
      "role": "Supplementary; required for attributing case-report findings",
      "role_reason": "This is needed to avoid attributing the course involving antibiotics, stenting, and acidification in a single case to recurrence prevention by a single-ingredient oral preparation.",
      "application_exception": "Do not present a descriptive title as the exact title of the original article or turn inferred composition into confirmed composition.",
      "criterion": "Preserve the acute course with concomitant treatments in 1 older man, different exposure after discharge, uncertainty about composition, and the title's status.",
      "basis": "M03 §3.2.1; detailed population criteria were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records were internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Separately verify the exposure timeline, concomitant interventions, composition confirmation, and acute dissolution versus long-term recurrence in the original case report, and assess the isolated contribution through an appropriate separate comparison."
    },
    {
      "item_id": "N30",
      "question_type": "Partial page and other treatments",
      "question": "Have the page actually verified in S10 and recurrence under other treatments been distinguished?",
      "needed": "Original S10 full text, populations/compositions by treatment, exposure, comparison/recurrence, and cited original reports",
      "role": "Supplementary; required for partial-reading status and attribution",
      "role_reason": "This is needed to avoid presenting a discussion of cystine treatment on a single page as verification of the entire full text or as a recurrence comparison of C alone.",
      "application_exception": "Do not count cited studies as new patients or assign recurrence values from other treatments to vitamin C.",
      "criterion": "Preserve partial verification of the abstract and p.1563 and the unverified comparison of C alone.",
      "basis": "The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; data collection/selection principles in M04 §4.5–4.6; the separation of access and reading and the hyperlink contract were internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M03 §3.2.4; internally defined limits on extension",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare original exposures, denominators, and recurrence by treatment and the cited families, and clearly record the page/full-text scope actually verified."
    },
    {
      "item_id": "N31",
      "question_type": "Review and search timing",
      "question": "What evidence map and time frame does the S11 review provide?",
      "needed": "S11 review full text, search end date/scope, original reference list, inclusion/exclusion, and funding",
      "role": "Supplementary; required for interpreting the review and timing",
      "role_reason": "This is needed to avoid counting the review as an independent new trial or as completion of a current exhaustive search.",
      "application_exception": "Even though the online publication on 2026-07-31 preceded the evidence cutoff date, it does not mean that all studies have currently been verified.",
      "criterion": "Preserve the review's map of urinary risks, the roles of the original trials, and the limitations of access and search scope.",
      "basis": "The distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application; M04 §4.5, §4.6.3; limits on the current data transformation reflect the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare the review's search end date and inclusion scope with the identities of the original reports, and update the observations in the corresponding row only when a new direct comparison has actually been acquired."
    },
    {
      "item_id": "N32",
      "question_type": "Registration shell and mirror identity",
      "question": "Have the registration leads in S15 and S16 been distinguished from the content actually verified?",
      "needed": "Complete official S15 registration/amendment history, original official S16 ID/version, protocols, and results",
      "role": "Supplementary; required for registration identity",
      "role_reason": "This is needed to avoid turning an official record shell and a 3rd-party mirror lead into an eligible completed trial or a negative search.",
      "application_exception": "Do not assume that NCT06989320 and the Carbon-13 oral-loading mirror are the same trial.",
      "criterion": "Record access failures involving the official shell, the mirror's status as a discovery lead, and the unverified ID at their respective locations.",
      "basis": "Data collection/selection principles in M04 §4.5–4.6; the separation of access and reading and the hyperlink contract were internally designed; M04 §4.5, §4.6.3; limits on the current data transformation reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify each lead's official identity, original version, population/exposure, recurrence endpoint, and result availability, and link them only after actually checking whether they are the same study."
    },
    {
      "item_id": "N33",
      "question_type": "Contrary results and differences between records",
      "question": "Are favorable/unfavorable results and bibliographic differences being mistaken for conflicts about the same effect?",
      "needed": "Actual contrasts, events/compositions, durations, bibliographic versions, and contrary/corrected material for each original report",
      "role": "Supplementary; required for interpreting contrary evidence and conflicts",
      "role_reason": "This is needed to avoid selectively retaining only favorable evidence or turning different outcomes into a statistical conflict about the same effect.",
      "application_exception": "If the other exact value underlying the publication-identity difference in S01 is unavailable, do not invent a new year or a correction event.",
      "criterion": "Distinguish the direct and indirect roles of unfavorable/favorable results from differences between records and unverified information.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses was internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare original populations, ingredients, contrasts, time points, and outcomes/versions to establish whether a conflict concerns the same question/analysis, and verify bibliographic corrections against original evidence."
    },
    {
      "item_id": "N34",
      "question_type": "Funding, provision, and independence",
      "question": "Have funding, product provision, roles, and conflicts of interest for the direct evidence been verified?",
      "needed": "Funding/conflicts of interest, internal support, product provision, and design/analysis/publication roles in original eligible reports",
      "role": "Required",
      "role_reason": "This is needed to avoid turning unverified information into absence of support or conflicts of interest, or into independent replication.",
      "application_exception": "The delivery package's default I1 designation is not an empirically verified finding of mixed funding. Do not create an independence score without eligible evidence.",
      "criterion": "Distinguish declarations actually read from unverified information, ineligible roles, and historical designations.",
      "basis": "Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not substantiate every detail of this item.",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify funding, product provision, and actual design/analysis/publication roles for the original eligible comparison, and separately disclose unverified items and the independence of linked families."
    },
    {
      "item_id": "N35",
      "question_type": "Hyperoxaluria and exposure changes",
      "question": "Have safety events in S01 been distinguished from comparative risk?",
      "needed": "S01 event definitions, exposure time, original flow of 2 people/24 people, comparator, dose reduction/discontinuation, and safety follow-up",
      "role": "Supplementary; required for interpreting harm signals",
      "role_reason": "This is needed to retain observed exposure changes without mistaking them for causal risk estimates or the proportion with any adverse event.",
      "application_exception": "Do not turn the 2 people with hyperoxaluria-related changes into 2 clinical new-stone events or a between-group risk difference.",
      "criterion": "Preserve the 1 discontinuation and 1 dose reduction, the noncomparative/mixed population, and the limitations concerning exposure duration.",
      "basis": "M19 §19.1.2–19.2.4; detailed distinctions were internally designed; design-specific harms questions in M19 §19.2; details of temporal relationships were internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Collect hyperoxaluria/clinical harms and discontinuations/dose reductions by group under the same formulation, exposure-time, and testing criteria, and disclose events together with exposed participant counts and time."
    },
    {
      "item_id": "N36",
      "question_type": "High-dose gastritis and age",
      "question": "Which population, dose, and duration does the report of gastritis-related discontinuation in S05 concern?",
      "needed": "S05 gastritis definition, flow of 3 people/17 people, adults/children, 5 g/day, duration, and other treatments/risks",
      "role": "Supplementary; required for retaining unfavorable harm findings",
      "role_reason": "This is needed to avoid omitting a safety report from a high-dose population with another stone type or transferring it to comparative risk in the target adults.",
      "application_exception": "Do not calculate the 3 discontinuations as a risk rate over a defined period in adults with calcium-oxalate stones.",
      "criterion": "Retain the 17 people with cystine stones, 5 g/day, and 3 gastritis-related discontinuations together with unverified age/duration and comparator information.",
      "basis": "M19 §19.1.2–19.2.4; detailed distinctions were internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify original ages, definitions of gastritis/discontinuation, exposure time, concurrent treatments, and events/denominators; study harms for the target formulation/population through separate comparative surveillance."
    },
    {
      "item_id": "N37",
      "question_type": "Intravenous label and limits of applicability",
      "question": "Have the warnings in the official injection label S12 been separated from oral evidence?",
      "needed": "Route/formulation, warnings, and at-risk populations in the original ASCOR label, and actual comparative data on oral harms",
      "role": "Supplementary; required for interpreting harms by route",
      "role_reason": "This is needed to preserve official warnings without transferring risk frequencies or efficacy from another route to this oral preparation.",
      "application_exception": "Warnings for a buffered intravenous scurvy preparation are neither event rates nor assurances of safety for a pure oral preparation.",
      "criterion": "Distinguish intravenous oxalate nephropathy/stones, renal function/dialysis/prior history, and the high-dose/intravenous G6PD context.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptation for testing were internally designed; M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundary. M19 principles are referenced; no formal causality tool was applied; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Verify route, formulation, at-risk populations, and event definitions in the official label, and study renal/hemolytic harms of the target oral exposure through separate exposure-specific comparisons and surveillance."
    },
    {
      "item_id": "N38",
      "question_type": "General upper limit, gastrointestinal effects, and iron",
      "question": "Have the general upper limit and harms in S13 been distinguished from an assurance of safety for stone patients?",
      "needed": "Upper limit/population and gastrointestinal/iron warnings in the NIH consumer material, and actual exposure-specific safety data in the target patients",
      "role": "Supplementary; required for interpreting upper limits and general harms",
      "role_reason": "This is needed to avoid mistaking the general adult upper limit for a safe prescribed dose or a no-harm threshold in stone patients.",
      "application_exception": "Do not represent reading the full consumer document as reading the health-professional page. Intake below the upper limit does not assure stone safety.",
      "criterion": "Preserve the total of 2,000 mg/day from all sources and the context of diarrhea/nausea/abdominal pain and iron overload.",
      "basis": "M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundary. M19 principles are referenced; no formal causality tool was applied; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Separately verify total dietary/supplemental exposure, stone history, and iron metabolism/symptoms, and assess patient-specific safety questions through actual exposure- and population-specific comparisons/surveillance."
    },
    {
      "item_id": "N39",
      "question_type": "Guideline caution and quantitative results",
      "question": "What outcome does the guidance to avoid excessive intake in S14 verify?",
      "needed": "Original EAU section, population, evidence/warnings, and actual comparative recurrence/harm data for the target oral formulation",
      "role": "Supplementary; required for interpreting guidelines",
      "role_reason": "This is needed to avoid turning guideline caution into a randomized recurrence effect or an individual safety assessment.",
      "application_exception": "Do not create a new threshold dose or a quantitative reduction in recurrence from statements about disputed risk and avoidance of excessive intake.",
      "criterion": "Preserve the context of advice to calcium-oxalate stone formers to avoid excessive intake and the unverified quantitative direct recurrence result.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations were internally designed; Chamgap's own interpretive boundary. M19 principles are referenced; no formal causality tool was applied; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Compare the original evidence cited by the guideline, formulation/population, and dose context, and assess quantitative recurrence/harm questions using actual comparative data."
    },
    {
      "item_id": "N40",
      "question_type": "Special populations and long-term gaps",
      "question": "Have gaps concerning renal risk, special populations, and long-term exposure been retained?",
      "needed": "Formulation- and route-specific data on renal risks, dialysis, prior oxalate stones/G6PD, iron, pregnancy/lactation, children, and long-term harms",
      "role": "Supplementary; required for limits on safety applicability",
      "role_reason": "This is needed to avoid treating populations with weak evidence or long-term high-dose exposure as safe on the basis of the general adult upper limit or data from other routes.",
      "application_exception": "This table is not an individual diagnosis, prescription, or safety assessment, and reported doses are not turned into recommended doses.",
      "criterion": "State the current caution, unverified information by population, route, and duration, and the separation of efficacy and safety.",
      "basis": "M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretive boundary. M19 principles are referenced; no formal causality tool was applied; M03 §3.2.1–3.2.4; details concerning dose, duration, and effect modification were internally designed; M19 §19.1.2–19.2.4; internal application",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "Prespecify special populations, independently monitor total exposure/duration, renal function/hemolysis/iron, and gastrointestinal/stone events, and disclose adequate follow-up and denominators."
    },
    {
      "item_id": "N41",
      "question_type": "Preservation of the original assessment and calculations",
      "question": "Have the current assessment and package/calculator designations been distinguished with their original values preserved?",
      "needed": "Original records of current grade/score, axes, primary_result, historical package/calculations, and editorial decisions",
      "role": "Required for preservation and traceability; not a condition establishing efficacy",
      "role_reason": "This is needed to avoid mistaking table production or a structural PASS for confirmation of a clinical grade or effect.",
      "application_exception": "Do not use the package's I1/EX/CX or the raw C from a format error as a valid new assessment, and do not fill empty values with 0.",
      "criterion": "Preserve the current ?, empty value, and Caution, the original designations, the absence of calculations, and the boundary that this is not independent verification.",
      "basis": "M04 §4.5, §4.6.3; limits on the current data transformation reflect the user-defined scope and internal design; Chamgap's own independence and attribution criteria. The official methods sections used in this pilot do not substantiate every detail of this item; M04 §4.6.3, M15 §15.3.1–15.3.3; the separation of statuses was internally designed",
      "condition_origin": "Individual criterion design and model review for a development case whose current retained content is known. These are not clinical preregistration or independent-validation criteria.",
      "proposed_research": "If new direct evidence is actually acquired, handle any update to the original assessment under separate authorization, versioning, and evidence review; this transformation table only links the original content and change events."
    }
  ]
}