{
  "title": "Vitamin B6: pyridoxine hydrochloride × Lower mean pain NRS in painful diabetic distal symmetric polyneuropathy",
  "criteria_version": "CG-GAP-v3097-main-1.0",
  "criteria_date": "2026-10-05",
  "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 of the intervention.",
      "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded 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 studies solely because results are unreported.",
      "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded 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": "Fix the outcome and effect of interest, and examine randomization, deviations, missingness, measurement and selective reporting.",
      "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded 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": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded 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": "Harm questions may require designs, populations and follow-up different from those for efficacy. Case reports do not establish incidence rates.",
      "review_level": "The retained record describes reuse of byte copies and SHA values of the original methods texts retained for the 1585 pilot. No new web/full methods-text reading or execution of the complete official tools was performed in that recorded review"
    }
  ],
  "status_dictionary": {
    "Verified": "The question within the specified retained materials and scope is verified; this does not establish efficacy or safety",
    "Partly verified": "Only some actual data have been verified, and the full condition remains unverified",
    "Unverified": "Direct data, methods or results could not be verified within the relevant scope; this does not mean no effect or no research",
    "Not met": "The actual intervention, population, endpoint/comparator in currently known materials does not match the fixed question; this is not a judgment of clinical ineffectiveness",
    "Not applicable": "An extension condition that does not apply to the current narrow question; not a substitute for external materials not read"
  },
  "schema_version": "chamgap-public-criteria-1.0",
  "condition_origin": "Chamgap’s own application conditions",
  "requirements": [
    {
      "item_id": "N01",
      "question_type": "Claim boundaries",
      "question": "Which population, intervention, comparator and pain outcome are being examined as a single question?",
      "needed": "The connection between the current /ko/effect and oral pyridoxine hydrochloride alone, adults with painful DSPN, placebo on the same background care and mean NRS.",
      "role": "Required",
      "role_reason": "Fixing this scope prevents categorical improvement or combination-product results from substituting for the NRS effect of monotherapy.",
      "application_exception": "If an actual monotherapy NRS study is verified, add its dose and duration with attribution to that study. Do not treat currently unverified dimensions as wildcards for all conditions.",
      "criterion": "Keep the subject of the judgment linked as recorded and fix the scope of monotherapy, diagnosis and between-group mean NRS. Leave other ingredients, conditions and scales in separate scopes.",
      "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed / M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "First screen studies that retain this question, and extract combinations, deficiency correction and other endpoints separately."
    },
    {
      "item_id": "N02",
      "question_type": "Ingredient and formulation",
      "question": "Do the actual study ingredient, route and formulation match the question about pyridoxine hydrochloride alone?",
      "needed": "The vitamer, salt and all active ingredients; oral route; and tablet release type, purity, batch and manufacturing origin.",
      "role": "Required",
      "role_reason": "Differences in vitamers, salts and combination composition directly affect attribution to a single ingredient.",
      "application_exception": "Do not fill in release type, purity or batch solely from a record that says tablets. Do not merge a PLP combination into the same intervention merely because it has the same vitamin name.",
      "criterion": "Distinguish oral pyridoxine hydrochloride alone from a PLP/B12/folate combination, and link only the formulation actually verified to the relevant study.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Verify the sole active ingredient of the investigational product and the placebo composition, then include only comparisons of that same product in the direct question."
    },
    {
      "item_id": "N03",
      "question_type": "Participant diagnosis",
      "question": "Were participants selected as having painful diabetic DSPN?",
      "needed": "Diagnostic and selection criteria for diabetes, distal symmetric neuropathy and pain; age, baseline pain and exclusion criteria.",
      "role": "Required",
      "role_reason": "A population with symptomatic diabetes cannot automatically be treated as the same eligible population as precisely diagnosed painful DSPN.",
      "application_exception": "Do not conclude that the population was different because the selection criteria were not read. If separate results for a mixed population become available, review only that scope.",
      "criterion": "Compare the actual participant diagnoses with the fixed question; do not establish eligibility for painful DSPN solely from the wording symptomatic diabetes.",
      "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Define diabetic distal symmetric neuropathy and pain in advance, and separate results for other neuropathies and populations treated to correct deficiency."
    },
    {
      "item_id": "N04",
      "question_type": "Deficiency and special populations",
      "question": "Are data available to distinguish correction of B6 deficiency from the separate questions concerning kidney disease, pregnancy and lactation?",
      "needed": "Assessment of baseline deficiency and participants by stratum; inclusion of participants by kidney function, pregnancy and lactation; and direct pain estimates.",
      "role": "Supplementary; required for extension to those populations",
      "role_reason": "Differences in baseline nutritional status and safety in special populations limit generalization of the NRS effect of monotherapy.",
      "application_exception": "Do not require studies of every special population for the narrow adult NRS question. Direct data are needed for claims extending to those populations.",
      "criterion": "Separate treatment solely to correct deficiency from the specified pain-efficacy question, and do not infer an analgesic effect solely from low B6 indices.",
      "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed / M19 §19.1.2–19.2.4; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Prespecify the deficiency-correction stratum, and examine effect modification by kidney function and other factors through separate estimates and interactions. Do not use this table to determine an individual’s dose."
    },
    {
      "item_id": "N05",
      "question_type": "Common background care",
      "question": "Are the actual comparator groups’ background care and placebo contents verified?",
      "needed": "Investigational-product and placebo composition; diet, medication, analgesics and rescue medication in both groups; and records of changes.",
      "role": "Required",
      "role_reason": "Needed to avoid wrongly attributing differences in concomitant or rescue medication to pyridoxine’s contribution to pain outcomes.",
      "application_exception": "Do not require every treatment change to be identical. Verify the actual effect of interest and how changes were handled in the analysis.",
      "criterion": "Link the actual content of background care and differences between groups, and do not infer that treatment was actually identical solely from instructions to maintain it.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Define background care in both groups and record medication changes and rescue use, linking them to interpretation of assignment and adherence effects."
    },
    {
      "item_id": "N06",
      "question_type": "Dose",
      "question": "Are the actual dose and administration schedule for an eligible mean NRS comparison verified?",
      "needed": "The connection between actual dose, frequency, total B6 exposure and the corresponding NRS result; identification of totals derived from historical schedules.",
      "role": "Required",
      "role_reason": "Distinguishing an adjacent schedule from a dose with direct efficacy evidence prevents data conversion from becoming a new prescribing claim.",
      "application_exception": "Do not fill in actual intake from a nominal schedule. Do not recalculate the original total or conflate it with nutritional upper limits or an efficacious dose.",
      "criterion": "Attribute only doses recorded in the original report to the relevant trial, and do not use the total from an adjacent schedule as a dose with established efficacy or a dosing recommendation.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Link a verified monotherapy dose only to its study results. Review claims about an optimal dose separately, only when direct dose comparisons are available."
    },
    {
      "item_id": "N07",
      "question_type": "Observation period",
      "question": "Are the measurement time point, treatment duration and post-discontinuation follow-up for eligible NRS results verified?",
      "needed": "Actual NRS collection time points; treatment, follow-up and discontinuation periods; and separate results on sustained effects.",
      "role": "Required",
      "role_reason": "Linking the endpoint to the observation period prevents old categorical observations from being read as sustained NRS effects.",
      "application_exception": "The current question does not require maintenance of the effect. Direct post-discontinuation follow-up is required only when extending the claim to sustained effects.",
      "criterion": "Do not transfer the adjacent 4-month categorical observation period to NRS assessment; leave post-discontinuation effects unverified when no data on them are available.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M03 §3.2.1–3.2.4; details of dose, persistence and effect modification are custom-designed",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Prespecify the NRS assessment window and end time point, and examine sustained effects through separate estimates after treatment ends."
    },
    {
      "item_id": "N08",
      "question_type": "Pain scale",
      "question": "Did an actual eligible study use a validated mean pain NRS?",
      "needed": "Scale name, range, direction and validity; collection procedures and time points; and the definition of mean pain.",
      "role": "Required",
      "role_reason": "Without matching scales, responder counts and differences in mean pain cannot be compared as the same outcome.",
      "application_exception": "Do not enter 0–10 as the NRS range actually used. Preserve other scales with their original values and definitions, without automatic conversion.",
      "criterion": "Verify the scale actually used. Distinguish the question’s preferred range of 0–10 from actual instrument use, and do not convert VAS, categories or NTSS-6 to NRS.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M03 §3.2.4; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Prespecify the validated NRS, collection window and direction, and report mixed pain-or-paresthesia categories separately."
    },
    {
      "item_id": "N09",
      "question_type": "Categorical scale",
      "question": "Are Levin’s −1/0/+1/+2 categories eligible as direct mean NRS results?",
      "needed": "The meaning of the original symptom categories, their pain/paresthesia composition and measurement differences from NRS.",
      "role": "Required",
      "role_reason": "Separating known ineligible scales prevents them from filling gaps in eligible pain-effect results.",
      "application_exception": "This Not met status applies only to the categorical results currently preserved. It does not deny the existence of separate results that have not been verified.",
      "criterion": "Use a result as a direct endpoint only when it is a validated mean NRS result. Do not interpret study-specific ordinal categories as an equal-interval continuous scale.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M03 §3.2.4; custom application / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract ordinal categories using their original definitions and check whether direct NRS results were reported separately. Do not invent means or standard deviations."
    },
    {
      "item_id": "N10",
      "question_type": "Responder counts",
      "question": "Do 6/9 versus 4/9 represent mean NRS or a 50% pain-response rate?",
      "needed": "The original response definition, pain/paresthesia composition, denominator for each response and distinction from mean pain outcomes.",
      "role": "Required",
      "role_reason": "Reading responder counts as a mean difference or as a different response criterion misattributes both the effect and the denominator.",
      "application_exception": "Do not delete favorable response records. Do not treat the original categorical result as an effect of 0 because it is ineligible for mean NRS.",
      "criterion": "Use a result as mean NRS or a prespecified 50% pain response only when it measures that outcome. Do not turn the substantial-symptom-improvement category into another measure.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Report mean pain and prespecified response measures separately, linking each result to its denominator."
    },
    {
      "item_id": "N11",
      "question_type": "Participant flow",
      "question": "Can the denominators for allocation, symptom response, completion, and NRS analysis be distinguished?",
      "needed": "Allocation and participant flow by group, symptom-response denominators, visit completion, and counts measured and analyzed for NRS.",
      "role": "Required",
      "role_reason": "Needed to avoid transferring a verified sample size to the analysis denominator for an unverified pain outcome.",
      "application_exception": "Do not state that there were no participants because a denominator is empty. Keep the McCann/Cohen denominators unverified in their separate candidate records.",
      "criterion": "Link only the originally provided denominator to its corresponding result; do not infer completion of all visits or the direct NRS analysis count from 18 participants and 9/9.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract allocation, measurement, completion, and analysis denominators for each endpoint/visit, without using them interchangeably."
    },
    {
      "item_id": "N12",
      "question_type": "Mean pain values",
      "question": "Can baseline, change, and endpoint mean NRS values be directly verified?",
      "needed": "Group-specific baseline, change, and endpoint NRS means, units, time points, and analysis populations.",
      "role": "Required",
      "role_reason": "The lack of available mean values is a key gap that prevents direct evaluation of the pain effect of interest.",
      "application_exception": "Do not use means of indirect biomarkers as NRS before obtaining eligible results. Do not conclude that the values are unreported anywhere in a full text that has not been read.",
      "criterion": "Each mean must be linked to an actual NRS measure, group, and time point. Do not fill these fields with general symptoms, nerve conduction, PLP, or fasting glucose.",
      "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract baseline, change, and endpoint values separately and specify in advance the between-group effect to be estimated."
    },
    {
      "item_id": "N13",
      "question_type": "Variance and error",
      "question": "Are the SD, SE, sample size, and type of error statistic for direct NRS results verified?",
      "needed": "Group-specific variances for NRS changes/endpoint values, the SD/SE labels and n, and covariance and model descriptions where needed.",
      "role": "Required",
      "role_reason": "Direct interpretation of significance or CIs is not possible without the original type of error statistic and denominator.",
      "application_exception": "Do not assign a new low-precision grade solely because variance is unavailable. Do not transfer values from an ineligible scale into NRS variance.",
      "criterion": "Verify the actual type of error statistic, endpoint, time point, and denominator; do not reconstruct unreported variance from categorical responses.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M15 §15.3.1–15.3.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract the original values while distinguishing SD from SE, and record the endpoint, time point, group, and denominator together. Do not insert arbitrary correlations or variances."
    },
    {
      "item_id": "N14",
      "question_type": "Between-group estimation",
      "question": "Are the between-group difference, CI, P value, and effect of interest for the fixed NRS question verified?",
      "needed": "Effects of assignment/adherence, the model, direction, CI, P value, and analysis denominator for the difference in changes or endpoint values.",
      "role": "Required",
      "role_reason": "A pain-effect estimate versus placebo cannot be constructed from mean values or counts of favorable responses alone.",
      "application_exception": "Do not interpret an uncalculated estimate as a finding of no difference. If the original P value is unavailable, do not label the result nonsignificant.",
      "criterion": "Link only actual between-group NRS estimates and intervals; do not fill gaps by calculating differences, CIs, or P values from within-group improvement or categorical responses.",
      "basis": "M08 §8.2.2, M15 §15.3.1; custom application / M15 §15.3.1–15.3.3; custom application / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Specify whether the effect of interest is the effect of assignment or adherence, and report baseline adjustment, handling of missing data, and the direction and CI of the between-group estimate."
    },
    {
      "item_id": "N15",
      "question_type": "Clinical importance",
      "question": "Is there an applicable threshold for an important difference with which to interpret the direct NRS effect?",
      "needed": "An MCID or justified important difference for the same population, scale, and assessment window, together with the interval for the direct effect.",
      "role": "Required",
      "role_reason": "Significance or participant counts alone cannot establish the clinical meaning of pain improvement.",
      "application_exception": "Do not fill the gap by proposing unsupported numerical thresholds. If no importance threshold is available, retain the manuscript's unverified status.",
      "criterion": "Compare thresholds supported by actual sources with direct NRS intervals. Do not invent universal minimum participant counts, durations, trial counts, or an arbitrary MCID.",
      "basis": "M15 §15.3.1–15.3.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Prespecify the evidence and scope of applicability for an important difference, and distinguish the magnitudes of benefit, no difference, and unfavorable effects compatible with the CI."
    },
    {
      "item_id": "N16",
      "question_type": "Allocation and design",
      "question": "Can actual allocation, concealment, and baseline balance be verified?",
      "needed": "Parallel/crossover/cluster structure, random-sequence generation and allocation-concealment procedures, and baseline characteristics by group.",
      "role": "Required",
      "role_reason": "Known allocation descriptions must be distinguished from unverified concealment and baseline balance to assess actual comparability.",
      "application_exception": "Do not preassign NA to crossover or cluster-design issues for a candidate whose design is unverified. A record of randomization does not automatically establish absence of bias.",
      "criterion": "Link the actual methods to their results, and do not mark allocation, concealment, or confounding issues as resolved on the strength of an RCT label alone.",
      "basis": "M08 §8.1–8.2.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Verify the actual parallel/crossover/cluster structure and link the handling of allocation, clusters, and periods for each design to the pain outcome of interest."
    },
    {
      "item_id": "N17",
      "question_type": "Assessment blinding",
      "question": "Are blinding and collection procedures for subjective pain assessment verified?",
      "needed": "Blinding of participants, care providers, and assessors; placebo appearance; NRS collection methods; and differences in measurement between groups.",
      "role": "Required",
      "role_reason": "Patient-reported pain must be reviewed in relation to the actual collection and blinding conditions.",
      "application_exception": "Do not treat inability to blind as an automatic failure. A double-blind label does not establish eligibility of direct NRS measurement.",
      "criterion": "Distinguish a double-blind description from actual pain-collection procedures, and do not assign successful blinding or absence of measurement bias without evidence.",
      "basis": "M08 Table 8.2.a, M03 §3.2.4; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Specify the NRS collection window, who collects it, handling of omissions, and identical procedures across groups, and examine actual limitations in blinding."
    },
    {
      "item_id": "N18",
      "question_type": "Adherence and rescue medication",
      "question": "Can actual adherence, analgesics, rescue medication, and treatment changes be verified?",
      "needed": "Actual intake and adherence by group, concomitant analgesics, rescue medication, treatment changes, and their handling in the analysis.",
      "role": "Required",
      "role_reason": "Deviations from treatment and other pain-relief interventions may explain differences in pain, so they need separate documentation.",
      "application_exception": "Do not require every change to be identical. The current unverified status does not establish nonadherence or unequal treatment.",
      "criterion": "Distinguish maintenance instructions from actual behavior, and link the handling of changes by group to their impact on the effect of interest.",
      "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Distinguish the effect of assignment from the effect of adherence, and report and analyze rescue medication and treatment changes in a prespecified manner."
    },
    {
      "item_id": "N19",
      "question_type": "Missing data and analysis populations",
      "question": "Are NRS missingness, dropouts, and the actual analysis populations and handling verified?",
      "needed": "Reasons for missing NRS data and dropouts at each visit, ITT/PP, analysis n, handling of missing data, and sensitivity analyses.",
      "role": "Required",
      "role_reason": "Missing data and actual analysis counts are directly needed to interpret mean pain estimates.",
      "application_exception": "Do not convert unverified missingness into confirmed attrition bias or 0 dropouts. Also retain the existence of ineligible categorical results.",
      "criterion": "Verify the original analysis population and endpoint-specific missingness, without inferring NRS ITT populations or completion counts from allocation counts or categorical denominators.",
      "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M08 §8.2.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract endpoint-specific missingness and reasons by group, and prespecify analysis and sensitivity methods appropriate to the effect of interest."
    },
    {
      "item_id": "N20",
      "question_type": "Plans and selective reporting",
      "question": "Can prespecified pain endpoints, analyses, and time points be compared with actual reporting?",
      "needed": "Registrations, protocols, and analysis plans for monotherapy candidates; pain-endpoint hierarchy, time points, multiplicity, and reasons for changes.",
      "role": "Required",
      "role_reason": "Comparison with actual plans is needed to avoid treating the current results gap as proof of selective reporting.",
      "application_exception": "An unavailable plan for an older trial is not proof that it was unregistered. Do not attach the registration of a different combination trial to a monotherapy candidate.",
      "criterion": "Compare only plans and results that have actually been obtained. Do not describe an unavailable plan as proof of nonregistration or selective reporting.",
      "basis": "M08 Table 8.2.a, M04 §4.6.3; custom application / M04 §4.5, §4.6.3; limits on the current conversion of the material reflect the user-defined scope and custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Compare prespecified pain endpoints, analyses, and time points with actual results, and separately record reasons for changes and multiple comparisons."
    },
    {
      "item_id": "N21",
      "question_type": "McCann candidate",
      "question": "Can the monotherapy, comparator, pain scale, and results of McCann 1983 be directly verified?",
      "needed": "The original article's methods, formulation/dose, comparator, population, pain instrument, and results/denominators, and their agreement with the review's citation.",
      "role": "Required",
      "role_reason": "Unverified monotherapy candidates must be retained to describe honestly the scope of the current direct-evidence gap.",
      "application_exception": "Do not present control and blinding mentioned in a title as verified details of the methods. A review's mention of a candidate does not establish that the full text was read or that direct results were obtained.",
      "criterion": "Do not use bibliographic titles or clues from reviews as original numerical results. Use full-text results to verify whether an eligible mean NRS was reported.",
      "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract use a custom design / M03 §3.2.1; detailed population conditions use a custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations use a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses uses a custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "If the full text is obtained, verify the population, monotherapy intervention, comparator, scale, and denominators, and record new reasons for inclusion/exclusion. Hold review-level numbers pending verification."
    },
    {
      "item_id": "N22",
      "question_type": "Cohen candidate",
      "question": "Can the pain instrument, comparator, and direct results of Cohen 1984 be verified?",
      "needed": "The original article's population, single-ingredient composition, design, pain instrument/time point, denominators, and results, together with the actual access history.",
      "role": "Required",
      "role_reason": "Retain its status as a separate candidate to avoid confusing failed access with negative pain findings.",
      "application_exception": "Do not label the absence of an external access attempt in this review as inaccessibility. Do not infer from original metadata alone that all the information is unreported in the full text.",
      "criterion": "Do not use PubMed metadata or the publisher403 record from that time as original results. Verify direct NRS eligibility after obtaining the results.",
      "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract use a custom design / M03 §3.2.1; detailed population conditions use a custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations use a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations use a custom design / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations use a custom design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses uses a custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "After obtaining the original text, screen the single ingredient, population, comparator, and scale, and link only the pain results that can actually be verified."
    },
    {
      "item_id": "N23",
      "question_type": "Study families and missing identities",
      "question": "Are all links between reports and actual study families verified?",
      "needed": "Correspondence between report IDs, DOI/PMID, families, and the original material list, and the identity of missing references.",
      "role": "Required",
      "role_reason": "Needed to distinguish report counts from study counts and avoid mistaking a missing reference for replicated numerical evidence.",
      "application_exception": "When a material's identity is missing, do not delete it or treat it as a confirmed entry in the actual material list. Do not convert the total family count into a count of direct NRS replications.",
      "criterion": "Do not add together an abstract, an author-provided full text, and a review of the same study; leave an ID absent from the list as an unverified link.",
      "basis": "M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result linkage is a custom application / M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Link report→study family→endpoint/timepoint/analysis, and manage missing IDs as provisional references until verified."
    },
    {
      "item_id": "N24",
      "question_type": "Metanx combination",
      "question": "Does Metanx provide a direct comparison of mean NRS for pyridoxine hydrochloride alone?",
      "needed": "Full PLP/folate/B12 composition, primary VPT/secondary NTSS-6, and results isolating the B6 contribution.",
      "role": "Required",
      "role_reason": "Needed to prevent misattribution to monotherapy while retaining favorable combination results.",
      "application_exception": "Do not label results for the combination as showing no effect. Do not convert VPT/NTSS-6 to NRS.",
      "criterion": "Include only when the specified monotherapy intervention and mean NRS are directly linked. Do not use combination results as direct effects when the contributions of other ingredients have not been separated.",
      "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation for each question is custom-designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M03 §3.2.4; custom limits on extensions",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Retain combination results by study family and separately check for monotherapy comparisons or comparisons isolating component contributions."
    },
    {
      "item_id": "N25",
      "question_type": "Metabolic and oxidative markers",
      "question": "Do Dawood's metabolic and oxidative-stress results directly answer the painful DSPN NRS question?",
      "needed": "The newly diagnosed T2DM/metformin population, actual pain diagnosis and endpoints, and a comparison of B6 alone.",
      "role": "Required",
      "role_reason": "Shared references to diabetes and vitamins alone do not justify treating metabolic markers as patient-reported pain outcomes.",
      "application_exception": "Do not erase the significance of the verified metabolic study. Do not conclude that other results are absent from an unread original.",
      "criterion": "Do not substitute oxidative-stress or metabolic results for the same pain outcome; verify alignment of the actual population, intervention and NRS.",
      "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation for each question is custom-designed / M03 §3.2.4; custom limits on extensions",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract biomarkers as separate outcomes and verify whether painful DSPN and direct NRS results were actually reported."
    },
    {
      "item_id": "N26",
      "question_type": "Uncontrolled foot pain",
      "question": "Is Bae's foot-pain improvement an eligible diabetes-specific NRS result versus placebo?",
      "needed": "A separately identified diabetic DSPN population, pain instrument, comparison group, denominator, timepoint and between-group estimate.",
      "role": "Required",
      "role_reason": "Before-and-after improvement and an effect versus placebo are different estimates, so the actual study design must be verified.",
      "application_exception": "Retain uncontrolled reports as well. Do not state that there was no improvement or that the monotherapy effect was 0 merely because there was no comparison.",
      "criterion": "Do not treat uncontrolled improvement in a mixed population as a control-adjusted effect; verify that the specified population and actual comparison align.",
      "basis": "M03 §3.2.1; detailed population conditions are custom-designed / M08 §8.1–8.2.3; custom application / M08 §8.2.2, M15 §15.3.1; custom application / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Retain mixed-population results within their original scope and check whether separate controlled results exist for the specified population."
    },
    {
      "item_id": "N27",
      "question_type": "Registry scope",
      "question": "Can the use of monotherapy, latest status and pain results for NCT04689971 be verified?",
      "needed": "Intervention composition, population, endpoints, status and results in the official registration, together with the extent to which the material has actually been obtained.",
      "role": "Required",
      "role_reason": "The existence of an official registry URL alone does not establish that results have been made public or read, or that the intervention is eligible as monotherapy.",
      "application_exception": "Do not treat a registry record that has not been obtained as evidence of no trial or a result of 0. Do not recast the historical shell record as a failure in this review.",
      "criterion": "Do not treat the indexed description and application shell as complete registry results. Do not link the B1/B6/B12 combination to B6 monotherapy.",
      "basis": "M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design / M08 Table 8.2.a, M04 §4.6.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Link registration, results and publication reports within study families, distinguishing planned information from actual results."
    },
    {
      "item_id": "N28",
      "question_type": "Guideline context",
      "question": "Can a direct NRS effect of B6 alone be verified from the ADA/AAN guidelines?",
      "needed": "The guidelines' actual recommendations and evidence links, and results from the relevant monotherapy pain trials.",
      "role": "Supplementary; essential for interpreting clinical context",
      "role_reason": "Needed to avoid conflating clinical recommendations with a specific ingredient's direct effect estimate.",
      "application_exception": "This table is not a guideline replacing existing pain treatment. Do not infer the absence of original studies solely from a guideline's list.",
      "criterion": "Distinguish guidelines used as clinical context from direct effect evidence; do not use absence from a recommendation list as evidence of no effect.",
      "basis": "M04 §4.5–4.6 provides principles for material collection/selection; separating access from reading and the hyperlink contract are custom-designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Check the studies underlying recommendations against the original question; do not use the absence of a recommendation as an exclusion reason or as an effect of 0."
    },
    {
      "item_id": "N29",
      "question_type": "Result direction and conflicting findings",
      "question": "Can the favorable, no-difference and unfavorable directions of unique eligible NRS results be compared together?",
      "needed": "Between-group NRS estimates and intervals from unique eligible trials, and differences in populations, interventions, timepoints and analyses.",
      "role": "Required",
      "role_reason": "Needed to avoid filling gaps with only favorable adjacent results or treating dissimilar results as conflicts.",
      "application_exception": "Do not turn statistical nonsignificance into an effect of 0 or equivalence. Differences across scales or populations do not automatically constitute conflicting data.",
      "criterion": "Compare only direct results addressing the same question; do not turn differences involving ineligible scales or unverified results into data conflicts or findings of no difference.",
      "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is custom-designed / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Attribute results in every direction to their study family, endpoint, timepoint and analysis, and record only actual conflicts concerning the same question, together with reasons."
    },
    {
      "item_id": "N30",
      "question_type": "Product supply and conflicts of interest",
      "question": "Can product supply, research funding, author conflicts of interest and independence be verified?",
      "needed": "Supply of the active agent and placebo, full funding, employment, patents, disclosed COI, and links to institutions/study families.",
      "role": "Supplementary; essential for claims of independence",
      "role_reason": "The actual scope of disclosures must be explained without treating product supply as independent funding or proof of bias.",
      "application_exception": "Do not discard results because of company involvement. Do not state that there are no conflicts of interest because disclosures could not be read.",
      "criterion": "Distinguish verified supply arrangements from unverified full funding and COI; do not automatically grant independence or automatically exclude company-related results.",
      "basis": "Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not validate all the details of this item / M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/result linkage is a custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract funding, product supply and author relationships from the original text, and review the independence claim and relevance to the results separately."
    },
    {
      "item_id": "N31",
      "question_type": "Neuropathy harms",
      "question": "Can harm events, denominators and collection methods be verified for the same exposure and population?",
      "needed": "Definitions, collection, severity and discontinuations relating to new/worsening sensory neuropathy, plus group-specific counts of people with events, exposure denominators and duration.",
      "role": "Supplementary; essential for interpreting safety",
      "role_reason": "Similar neuropathy symptoms can be treatment targets and harm events, so separate verification is needed.",
      "application_exception": "Do not remove efficacy data because harms were not reported. Do not expand the finding into a claim that all food intake is dangerous or that this trial established harm.",
      "criterion": "Do not use official warnings as incidence or causal estimates from efficacy trials; link actual events and denominators for the same exposure/population with their limitations.",
      "basis": "M19 §19.1.2–19.2.4; custom application / M19 §19.1.2–19.2.4; detailed distinctions are custom-designed / M19 §19.1.2–19.2.4, M04 §4.6.3; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Define new/worsening events separately from efficacy, and collect information on those exposed, counts of people with events, duration and discontinuations. Distinguish spontaneous reports from incidence."
    },
    {
      "item_id": "N32",
      "question_type": "Timing of harms and recovery",
      "question": "Can the minimum dose and duration associated with risk of harm, and recovery after discontinuation, be verified?",
      "needed": "Timing of exposure initiation, duration, event onset/worsening, discontinuation and recovery, with the relevant population and products.",
      "role": "Supplementary; essential for claims about timing and safety thresholds",
      "role_reason": "Needed to avoid turning gaps in temporal relationships into a safe dose or a guarantee of recovery.",
      "application_exception": "Do not create a new probability of permanent damage from a lack of improvement after discontinuation. An unverified minimum dose associated with risk does not mean equal risk at every dose.",
      "criterion": "Link only verified temporal relationships; do not estimate a minimum threshold, complete recovery or recovery timing.",
      "basis": "M19 §19.2 addresses harm questions by study design; temporal-relationship details are custom-designed / M19 §19.1.2–19.2.4; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Extract temporal sequence and the course after discontinuation from individual records; do not extrapolate recovery or thresholds beyond the observation period."
    },
    {
      "item_id": "N33",
      "question_type": "Overlapping exposures and causes",
      "question": "Can all B6 products, concomitant medicines and other causes of symptom worsening be verified?",
      "needed": "Total exposure by food, supplements/medicines and vitamers, concomitant medicines, underlying disease, and alternative causes of new/worsening symptoms.",
      "role": "Supplementary; essential for extensions to causality and individual safety",
      "role_reason": "Distinguishing tingling as a target of efficacy from supplementation-related harm requires verification of concurrent exposures and alternative causes.",
      "application_exception": "Do not decide on an individual's products or treatment in the current data conversion. Do not state that other causes were absent because information on alternatives is unavailable.",
      "criterion": "Separately verify the effects of multiple products and underlying disease; do not automatically attribute symptom worsening to diabetes or a single product.",
      "basis": "M19 §19.2.2–19.2.4 provides design considerations; detailed recording of confounding is custom-designed / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied / M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / M19 §19.1.2–19.2.4; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Distinguish new onset from worsening of the same symptoms and limit causal interpretation to the verified scope of all B6 products, concomitant medicines and underlying causes."
    },
    {
      "item_id": "N34",
      "question_type": "Upper limits and regulatory timing",
      "question": "Can current official nutritional upper limits, the scope of preparations and implementation status be verified?",
      "needed": "Sources and populations for US/EFSA nutritional upper limits, the Australian scope of preparations, effective dates and the original cutoff date.",
      "role": "Supplementary; essential for nutritional and regulatory interpretation",
      "role_reason": "Timing and the nature of each figure must be distinguished so that upper limits or regulatory figures are not misread as doses with verified efficacy or thresholds of no risk.",
      "application_exception": "No new checks of legislation or official websites are performed in this review. Do not describe a historical planned date as current implementation.",
      "criterion": "Distinguish the different nutritional and regulatory information at the original cutoff date; do not use it as an effective pain-treatment dose, a safe dose or verification of current law.",
      "basis": "M04 §4.5, §4.6.3; limits on the current data conversion follow the user-defined scope and custom design / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are custom-designed / M19 §19.1.2–19.2.4; custom application / Chamgap's own interpretation limits. M19 principles are referenced; no official causality tool was applied",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "When updating official information, verify legislation, nutritional standards and treatment effects separately while retaining the original cutoff-date record."
    },
    {
      "item_id": "N35",
      "question_type": "Long-term and vulnerable-group safety",
      "question": "Are there direct safety data on long-term/rare harms and vulnerable groups?",
      "needed": "Long-term/rare events in the same population at the actual dose/duration, and exposure in kidney disease, pregnancy and lactation, with denominators/follow-up.",
      "role": "Supplementary; essential for long-term safety and safety in vulnerable groups",
      "role_reason": "Needed to avoid extending data from short-term observation or limited populations to overall safety.",
      "application_exception": "Not every study of rare harms is required as an efficacy condition for the current narrow NRS question. Broader safety claims require direct data.",
      "criterion": "Do not extend short observations of adjacent efficacy or nutritional upper limits to long-term safety or safety in vulnerable groups.",
      "basis": "M19 §19.1.2–19.2.4; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Use a design for harm collection and follow-up separate from the efficacy trial, and specify the limitations of the population, duration and denominators. Interpret the absence of rare events only within the scope of complete collection."
    },
    {
      "item_id": "N36",
      "question_type": "Material review",
      "question": "Are the historical access level of each material and the scope actually read on this occasion distinguished?",
      "needed": "The access_level and location in retained citations/evidence, actual current material types, access/acquisition, reading, dates and safe links.",
      "role": "Required",
      "role_reason": "The scope of materials actually read must be recorded accurately so that a blue summary link is not mistaken for verification of the full clinical text.",
      "application_exception": "The existence of a document or URL does not mean access succeeded. Do not label a full text as inaccessible merely because its public availability could not be verified.",
      "criterion": "Mark only the local retained summaries read on this occasion as read, and leave external materials as unattempted and unread. If an individual access date is absent, record an empty value.",
      "basis": "M04 §4.5–4.6 principles for material collection/selection; separation of access from reading and the hyperlink contract are a custom design / M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "For newly acquired materials, record the sections actually read and dates by material type, and keep retained summaries and full texts as separate items."
    },
    {
      "item_id": "N37",
      "question_type": "Search and preservation scope",
      "question": "Within which search, date and input scope was the direct result not verified?",
      "needed": "The original evidence cutoff and documented scope of search, selection and access, the files actually read now, and unacquired logs/registrations.",
      "role": "Required",
      "role_reason": "The dates and inputs underlying statements of absence must be limited so that material conversion is not overstated as an up-to-date comprehensive literature review.",
      "application_exception": "Incomplete searching or registry access is not evidence that no studies exist. Do not assume that the contents of a separate file have been read now.",
      "criterion": "Explain what remains unverified within the checked scope, and do not extend the absence of a new search or historical access limitations into a claim of 0 studies or worldwide absence of literature.",
      "basis": "M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design / M04 §4.5–4.6 principles for material collection/selection; separation of access from reading and the hyperlink contract are a custom design / M08 Table 8.2.a, M04 §4.6.3; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "In future evidence updates, record the actual search queries, dates, selection reasons and access failures, and link them to the current table as a separate version."
    },
    {
      "item_id": "N38",
      "question_type": "Preservation of the original judgment",
      "question": "Are the original ?, empty values, B/P and the limited meaning of no_human_study preserved?",
      "needed": "The original grade, score, axes, strengths/calculation status, and endpoint-scoped interpretation of no_human_study.",
      "role": "Required",
      "role_reason": "The historical judgment must be distinguished from the data-verification status in the table so that empty values are not changed into a score of 0 or an absence of effect.",
      "application_exception": "Do not run the original calculator or recalculate the grade. Do not isolate the no_human_study label and interpret it as an absence of all research.",
      "criterion": "Preserve the original values exactly, and do not use the B/P question classification as fulfillment of a result condition or a new score. A count of 0 directly eligible results does not mean 0 human studies or an effect of 0.",
      "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of results to each question is a custom design / M04 §4.5, §4.6.3; limits of the current material conversion follow the user-defined scope and custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "When eligible evidence is updated, first compare the material identity and endpoints. Do not add the statuses in this table to the existing calculator score."
    },
    {
      "item_id": "N39",
      "question_type": "Independent replication",
      "question": "Can independent replication of directly eligible monotherapy NRS studies be verified?",
      "needed": "Unique trials/report families, direct NRS results, denominators, institutions, funding and differences in conditions.",
      "role": "Required",
      "role_reason": "The existence of material families and independent replication of monotherapy NRS results are different facts.",
      "application_exception": "Do not replace unverified eligible families with NA for between-study comparison. Preserve both the existence of human studies and the count of directly verified results.",
      "criterion": "Do not use the number of reports, the 7 adjacent families or reviews as the number of directly eligible studies or as independent replication.",
      "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; linking cohorts/results is a custom application / Chamgap’s own independence and attribution conditions. The official methods sections used for this pilot do not warrant every detail of this item / M04 §4.6.1–4.6.2, M15 §15.3.1; custom application",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "After linking reports from the same trial, compare the conditions and directions of actual unique eligible results, and leave unverified study/participant counts as empty values."
    },
    {
      "item_id": "N40",
      "question_type": "Extension to other clinical outcomes",
      "question": "Does the pain NRS question require outcomes of neural recovery, disease prevention or mortality?",
      "needed": "Separate outcome definitions for mean pain and for nerve conduction, PLP, blood glucose, function and disease events.",
      "role": "Supplementary; essential for extended claims",
      "role_reason": "Needed to avoid unnecessarily requiring other clinical endpoints for the narrow pain question or extending numerical improvement to effects on clinical events.",
      "application_exception": "Do not reuse this NA for a claim about another clinical effect. Keep harm conditions separate.",
      "criterion": "The current independent question concerns mean pain NRS, so other clinical events are not imposed as essential conditions for fulfilling that question. Extended claims require separate direct data.",
      "basis": "M03 §3.2.4; custom boundary on extension / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are a custom design / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of results to each question is a custom design",
      "condition_origin": "Chamgap custom design and individual model review. These conditions adapt C/E/H principles to this question; they do not represent execution of an official tool or clinical certification",
      "proposed_research": "Design pain scores and neural function/disease events as different questions, and verify each endpoint, duration and denominator independently."
    }
  ],
  "language": "en",
  "translation_date": "2026-11-02"
}