{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3105-main", "verdict_number": "3105", "title": "Biotin — sole-added-active oral product × Lower HbA1c in adults with type 2 diabetes", "view_version": "1.0", "view_created_date": "2026-11-03", "criteria_version": "NGM-v3105-SOLE-BIOTIN-T2D-HBA1C-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Stored Korean and English manuscripts and case-specific criteria and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No external clinical abstracts, full texts, registry records or analysis plans were newly read. Historical access records are distinguished from the stored summaries read in this review. The original verdict, numerical values and unverified items are preserved; no new search, calculation or reassessment was performed.", "date_meaning": "This is the date the stored materials were checked, not the date of an up-to-date clinical literature search." }, "claim_context": { "population": "Adults with type 2 diabetes; confirmed deficiency correction, type 1, gestational and drug-induced diabetes, prediabetes and healthy populations are separate; unreported biotin status is not presumed normal", "intervention": "Biotin (biotin, vitamin B7), sole added active ingredient · The question is bounded to an oral product with a sole active ingredient; eligible product formulation, excipients, batch and purity are unverified · Oral; topical and injectable routes excluded", "dose": "Unverified — dose, frequency, dietary intake and total concurrent supplemental intake for an eligible regimen", "comparator": "Placebo, no biotin supplement or usual care under the same background conditions; the actual eligible comparator is unverified. Maintaining common diabetes treatment is a separate condition", "endpoint": "Priority is given to the between-group HbA1c change difference (%p) at a prespecified follow-up; an appropriately adjusted between-group endpoint contrast is separate. FPG, PPG, insulin, HOMA-IR and fructosamine are not substitutes", "duration": "Unverified — eligible treatment duration and prespecified HbA1c follow-up", "excluded_extensions": "Common metformin is allowed; mixtures with a concurrent change in chromium, confirmed deficiency correction, type 1/gestational/healthy populations, FPG/PPG/Hb and clinical events/assay bias are separate. The candidate GUTERRING biotin-only arm is retained. /subclaims=[]" }, "requirements": [ { "item_id": "N01", "question_type": "Independent claim", "question": "Which biotin, population and HbA1c comparison does the question concern?", "needed": "Adults with T2D · Oral biotin as the sole addition · Comparator with identical background conditions · Between-group HbA1c result at a prespecified time point", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid combining the ingredient as a whole or all glycemic markers into a single result.", "application_exception": "Type 1/gestational/healthy populations, confirmed deficiency correction, topical/injectable routes and concurrent changes in chromium are separate.", "criterion": "Link the current original effect wording to the actual inclusion/exclusion boundaries and original pointers.", "basis": "Question-clarification principles 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 adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "For each source, compare the direct comparison results that match this question and the reasons for any mismatch.", "current_reports": [ "S01", "S02", "S04", "S05", "S10", "S11", "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The selected question asks whether oral biotin as the sole added active ingredient in adults with T2D lowers HbA1c at a prespecified follow-up compared with placebo, no supplement or usual care under identical background treatment. subclaims is an empty list.", "condition_status": "Met", "status_reason": "This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide.", "missingness": "This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide.", "uncertainty": "This verifies the boundary; it does not establish efficacy or conclude that studies are absent worldwide.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Adults with T2D · Oral biotin as the sole addition · Comparator with identical background conditions · Between-group HbA1c result at a prespecified time point" }, { "item_id": "N02", "question_type": "Common treatment", "question": "Does common metformin treatment exclude a comparison of a sole added ingredient?", "needed": "Background treatment in both arms, added ingredients, arm-specific changes/rescue treatment and the actual effect of interest", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Common treatment must be distinguished from active ingredients that change concurrently.", "application_exception": "A comparison of biotin as the sole addition is not excluded merely because it is described as concomitant treatment.", "criterion": "Distinguish the difference in added ingredients from common treatment and link this distinction to endpoint eligibility.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare results in which only biotin differs under identical background treatment, along with changes in diabetes medications.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S11 is a candidate in which only biotin was added to the common treatment of metformin 500 mg/day in both arms, so it is not excluded because of concomitant treatment. The endpoint actually verified is not HbA1c.", "condition_status": "Met", "status_reason": "This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained.", "missingness": "This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained.", "uncertainty": "This verifies the preservation of common-treatment information; it does not mean that an actual eligible HbA1c comparison has been obtained.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Background treatment in both arms, added ingredients, arm-specific changes/rescue treatment and the actual effect of interest" }, { "item_id": "N03", "question_type": "Product identity", "question": "Are the chemical form, origin and manufacturer of the directly eligible product known?", "needed": "Exact chemical form, origin, manufacturer and documentation verifying the active ingredient", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid filling in the identity of an eligible HbA1c regimen with a product from another study.", "application_exception": "Naming biotin in the question does not verify the chemical form of the actual preparation.", "criterion": "Separate verified values for the directly eligible product from null values and reasons for nonverification.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Obtain and link the original product documentation and manufacturing specifications for the eligible result.", "current_reports": [ "S01", "S02", "S04", "S11", "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "exact_chemical_form and manufacturing_origin have null value entries/not_verified. source_part also leaves the chemical form, origin and manufacturer of the eligible preparation unverified.", "condition_status": "Unverified", "status_reason": "The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted.", "missingness": "The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted.", "uncertainty": "The product identity for a directly eligible HbA1c comparison could not be verified. Products from other trials are not substituted.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Exact chemical form, origin, manufacturer and documentation verifying the active ingredient" }, { "item_id": "N04", "question_type": "Formulation and quality", "question": "Are tablet/capsule form, excipients, brand, batch and purity verified?", "needed": "Formulation, excipients, brand, batch/purity and other added active ingredients", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid claiming identical composition and quality based solely on a product name.", "application_exception": "Specifications of a combination product are not transferred as verification of a sole-active product.", "criterion": "Identify the actual locations verifying the eligible formulation and composition/quality, or mark them as unverified.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the preparation specifications and batch documentation for the eligible comparison.", "current_reports": [ "S01", "S02", "S04", "S11", "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "tablet_or_capsule, excipients, brand and batch_purity all have null values/not_verified. An oral product with a sole active ingredient is the question boundary, not the specifications of an actual eligible product.", "condition_status": "Unverified", "status_reason": "Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available.", "missingness": "Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available.", "uncertainty": "Beyond the shared ingredient name, no direct information on formulation, excipients or quality is available.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Formulation, excipients, brand, batch/purity and other added active ingredients" }, { "item_id": "N05", "question_type": "Dose", "question": "What are the eligible biotin dose, frequency and total exposure?", "needed": "Eligible dose/frequency, dietary biotin, concurrent supplements and actual exposure", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid using quantities from adjacent FPG studies or safety cases as an HbA1c regimen.", "application_exception": "Do not arbitrarily convert values expressed in mg, µmol and µg at different source locations into mass equivalents.", "criterion": "Explain what is verified and what is missing about the actual dose and total exposure linked to the selected result.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details of dose, duration and effect modification are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Link the relevant product, dose, frequency and dietary/supplement records to the eligible result.", "current_reports": [ "S01", "S02", "S05", "S06", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "dose, frequency, dietary_biotin and concurrent_supplements have null values/not_verified for the directly eligible comparison. S11's 5 mg 2 times daily is the exposure in a candidate study of another endpoint.", "condition_status": "Unverified", "status_reason": "The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials.", "missingness": "The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials.", "uncertainty": "The eligible dose was not inferred from S11, chromium-combination products or assay-interference materials.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Eligible dose/frequency, dietary biotin, concurrent supplements and actual exposure" }, { "item_id": "N06", "question_type": "Duration and follow-up", "question": "Have the treatment duration and HbA1c follow-up time been specified?", "needed": "Actual treatment duration, prespecified follow-up time and separate post-discontinuation time point", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid transferring FPG at 4/6 weeks or a combination product at 90 days into the same HbA1c time point.", "application_exception": "Do not arbitrarily adopt a common minimum treatment duration.", "criterion": "Link the eligible treatment duration and prespecified HbA1c follow-up to the original plan/results.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application; M03 §3.2.1–3.2.4; details of dose, duration and effect modification are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the direct comparison's plan, treatment duration and results at each follow-up time point together.", "current_reports": [ "S05", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "treatment_duration and followup_time have null values/not_verified. S11 used 4 weeks of biotin treatment followed by 2 weeks of observation off biotin, while S05 used a combination product for 90 days; neither fills in the eligible HbA1c duration.", "condition_status": "Unverified", "status_reason": "The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long.", "missingness": "The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long.", "uncertainty": "The eligible duration and time point are unverified; this is not a conclusion that the treatment has no effect because its duration is short or long.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual treatment duration, prespecified follow-up time and separate post-discontinuation time point" }, { "item_id": "N07", "question_type": "Actual population", "question": "Are confirmed T2D diagnosis, baseline HbA1c and disease duration verified?", "needed": "Diagnostic criteria, age, baseline HbA1c, disease duration and population composition", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid filling in the actual baseline status of the eligible sample from the population label alone.", "application_exception": "Type 1, gestational and drug-induced diabetes, prediabetes and healthy populations are retained as separate questions.", "criterion": "Link the actual eligible population/baseline composition to the unverified items.", "basis": "M03 §3.2.1; detailed population criteria are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare recruitment, diagnosis, baseline tables and population composition for the eligible result.", "current_reports": [ "S01", "S02", "S04", "S10", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The question concerns adults with T2D, but diagnostic_criteria, baseline_HbA1c and disease_duration have null values for the directly eligible comparison. Materials on other populations are retained, with direct attribution restricted.", "condition_status": "Unverified", "status_reason": "An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison.", "missingness": "An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison.", "uncertainty": "An adjacent study recording baseline glycated hemoglobin is distinct from the target direct follow-up HbA1c comparison.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Diagnostic criteria, age, baseline HbA1c, disease duration and population composition" }, { "item_id": "N08", "question_type": "Biotin status", "question": "Have observations of low biotin been recast as confirmed deficiency correction?", "needed": "baseline_biotin, deficiency_assay, deficiency definition and eligible status", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish blood-level observations, unreported status and treatment of confirmed deficiency.", "application_exception": "Unreported status is not presumed normal, and a trial is not described as treating deficiency solely because low levels were observed.", "criterion": "Separate the status verified by the original source from the level of diagnosis that remains unverified.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Link the deficiency definition/assay to the direct HbA1c results for each relevant population.", "current_reports": [ "S01", "S02", "S04" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "baseline_biotin and deficiency_assay have null values for the eligible comparison. The original KO explicitly states that observations of low circulating biotin were not recast as a trial treating confirmed deficiency.", "condition_status": "Partly verified", "status_reason": "The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified.", "missingness": "The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified.", "uncertainty": "The exclusion/inclusion boundaries were preserved, but the biotin status of the actual eligible population remains unverified.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "baseline_biotin, deficiency_assay, deficiency definition and eligible status" }, { "item_id": "N09", "question_type": "Endpoint definition", "question": "Were between-group HbA1c changes distinguished from other glycemic outcomes?", "needed": "Prespecified between-group HbA1c change difference in %p, adjusted endpoint contrast and measurement/analysis definitions", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid interpreting FPG/PPG, insulin, HOMA-IR, fructosamine or Hb as HbA1c.", "application_exception": "Do not automatically equate an adjusted endpoint contrast with a change difference.", "criterion": "Attribute observations to the selected endpoint, unit, time point and analysis.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the original plan with the change/endpoint estimates in the actual HbA1c tables.", "current_reports": [ "S01", "S02", "S04", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "Priority is given to the between-group HbA1c change difference (%p), and an appropriately adjusted between-group endpoint contrast is separate. The original crux/content block and facets rule out substitution with FPG, PPG or other metabolic markers.", "condition_status": "Met", "status_reason": "This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained.", "missingness": "This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained.", "uncertainty": "This verifies the endpoint boundary; it does not mean that a direct estimate has been obtained.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Prespecified between-group HbA1c change difference in %p, adjusted endpoint contrast and measurement/analysis definitions" }, { "item_id": "N10", "question_type": "Measurement method", "question": "Are the HbA1c assay method and red-cell-related factors verified?", "needed": "HbA1c assay, interference, anemia/RBC lifespan, transfusion/Hb variants and renal function", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish changes in measured values from assay/red-cell conditions.", "application_exception": "Biotin interference in specific immunoassays is not generalized to all HbA1c methods.", "criterion": "Explain the actual assay method and arm-specific measurement conditions for the selected HbA1c outcome, and what remains unverified.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the assay principles, validation materials and baseline hematological/renal records for the eligible result.", "current_reports": [ "S01", "S02", "S04", "S06", "S07", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "HbA1c_assay, HbA1c_interference, anemia_RBC_lifespan, transfusion_hemoglobin_variant and renal_function have null values/not_verified.", "condition_status": "Unverified", "status_reason": "Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review.", "missingness": "Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review.", "uncertainty": "Interference in the assay itself or between-arm differences in anemia could not be verified within the scope of the retained materials in this review.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "HbA1c assay, interference, anemia/RBC lifespan, transfusion/Hb variants and renal function" }, { "item_id": "N11", "question_type": "Direct result", "question": "Is there an eligible between-group HbA1c estimate for biotin alone?", "needed": "Directly eligible between-group HbA1c effect, follow-up time point, denominator and original result location", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish the existence of related human studies from obtaining a direct result for this question.", "application_exception": "Failure to verify a direct result is not described as an effect of 0 or an absence of human studies worldwide.", "criterion": "Link the direct estimate or an explicit gap within the currently verified scope.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and internal design; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify the between-group effect and its definition/time point in the eligible original result.", "current_reports": [ "S01", "S02", "S04", "S05", "S11", "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "between_group_effect, P and CI have null values for the directly eligible comparison. The assessment's direct_eligible_human_result_verified=false is a bounded gate for the fixed question. related_human_studies_exist=true is also retained.", "condition_status": "Unverified", "status_reason": "Positive combination-product and FPG results are not substituted, and null values are not converted to 0.", "missingness": "Positive combination-product and FPG results are not substituted, and null values are not converted to 0.", "uncertainty": "Positive combination-product and FPG results are not substituted, and null values are not converted to 0.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Directly eligible between-group HbA1c effect, follow-up time point, denominator and original result location" }, { "item_id": "N12", "question_type": "Intervals and importance", "question": "Can the effect magnitude be interpreted using CI, P and MCID?", "needed": "Direct effect, confidence interval, variance, denominator and justified importance threshold", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid equating a P value with clinical importance or precision.", "application_exception": "Do not arbitrarily set a minimum sample size, number of trials or numerical HbA1c importance threshold.", "criterion": "Distinguish reported direct intervals/importance thresholds from the reasons interpretation is not possible.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M15 §15.3.1–15.3.3; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the direct result's estimate, CI and basis for the MCID together.", "current_reports": [ "S05" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "CI, P and MCID all have null values/not_verified for the eligible HbA1c comparison. P=.03 for the chromium-combination product is not used to construct an interval or importance assessment for biotin alone.", "condition_status": "Unverified", "status_reason": "This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence.", "missingness": "This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence.", "uncertainty": "This is nonverification of the source data, not evidence of an unimportant effect, a definitive finding of imprecision or evidence of equivalence.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Direct effect, confidence interval, variance, denominator and justified importance threshold" }, { "item_id": "N13", "question_type": "Denominators and analysis", "question": "Are the allocation, completion, analysis and ITT/PP denominators linked?", "needed": "Direct randomized/completed/analysis n, ITT/PP and reasons for/handling of missing data", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid using allocation or completion counts from another endpoint as HbA1c denominators.", "application_exception": "Do not sum n across different reports or arbitrarily reconcile flowchart conflicts.", "criterion": "Show the actual denominator and handling for the relevant HbA1c outcome, or mark them as unverified.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "For each eligible result, compare the recruitment→allocation→completion→analysis flow and handling of missing data.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "randomized_n, completed_n, analysis_n and ITT_PP have null values for the directly eligible comparison. S11's 60 allocated participants, 28 and 26 completers by arm, and 60 participants in the flowchart are records for other endpoints.", "condition_status": "Unverified", "status_reason": "An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants.", "missingness": "An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants.", "uncertainty": "An unspecified analysis in the original source is not filled in as ITT or as an HbA1c analysis of all participants.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Direct randomized/completed/analysis n, ITT/PP and reasons for/handling of missing data" }, { "item_id": "N14", "question_type": "Design and allocation", "question": "Are allocation, concealment and baseline balance known for the direct HbA1c result?", "needed": "Actual eligible comparison design, randomized/nonrandomized allocation, concealment and baseline balance", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid transferring a description of an adjacent randomized study as verification of the design for the selected HbA1c result.", "application_exception": "An unverified design is not labeled as crossover/cluster inapplicability or an automatic failure on bias.", "criterion": "Distinguish the verified design information for the selected result from the scope that remains unverified.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M08 §8.1–8.2.3; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the protocol/allocation documents and baseline tables for the direct comparison.", "current_reports": [ "S02", "S04", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The retained evidence reports adjacent designs, including randomized blinded studies in S02/S04 and a single-center computer-randomized open-label trial in S11. The link between a directly eligible HbA1c result and its design is unverified.", "condition_status": "Unverified", "status_reason": "The reference to trial_families.json in evidence does not mean that the file was read in this review.", "missingness": "The reference to trial_families.json in evidence does not mean that the file was read in this review.", "uncertainty": "The reference to trial_families.json in evidence does not mean that the file was read in this review.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Actual eligible comparison design, randomized/nonrandomized allocation, concealment and baseline balance" }, { "item_id": "N15", "question_type": "Adherence and rescue treatment", "question": "Are actual adherence, diabetes medication changes, diet and exercise known?", "needed": "adherence, background meds, rescue/change, diet/exercise and handling in the analysis", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to separate concurrent changes from biotin's contribution.", "application_exception": "Verify the actual effect of interest and the handling methods rather than requiring all changes to be identical.", "criterion": "Explain arm-specific concurrent changes and adherence in the eligible comparison, and the gaps.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Link adherence, rescue-treatment and arm-specific change records for the eligible original result.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "adherence, background_diabetes_medication, medication_change_rescue and diet_exercise have null values/not_verified for the directly eligible comparison. These are separate verification items from the nominal common metformin exposure in S11.", "condition_status": "Unverified", "status_reason": "Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study.", "missingness": "Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study.", "uncertainty": "Concurrent changes/handling needed for an actual incremental-effect analysis were not filled in solely from a nominal regimen in an adjacent study.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "adherence, background meds, rescue/change, diet/exercise and handling in the analysis" }, { "item_id": "N16", "question_type": "Planning and selective reporting", "question": "Were the planned HbA1c outcome, analysis and time points compared with what was reported?", "needed": "Registry record text, history, protocol, SAP, actual results and reasons for changes", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish a registry shell from verification of the original plan.", "application_exception": "Failure to obtain material is not recast as confirmed nonregistration or selective reporting.", "criterion": "Identify the locations showing what was actually compared and the plans/time points not compared.", "basis": "Data collection/selection principles 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 material conversion follow the user's scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the eligible candidate's registry history and original plan with the actual results.", "current_reports": [ "S13", "S14", "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S13/S14 are registry shells, and S15 is an indexed excerpt/shell. The historical limitation that some registry record texts, histories, protocols and SAPs could not be adequately obtained is explicitly stated in KO.", "condition_status": "Partly verified", "status_reason": "Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0.", "missingness": "Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0.", "uncertainty": "Having a registration number/link does not mean that the prespecified HbA1c plan has been verified. External lookups in this review: 0.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Registry record text, history, protocol, SAP, actual results and reasons for changes" }, { "item_id": "N17", "question_type": "Adjacent sole-biotin treatment", "question": "Were Maebashi's fasting-glucose findings transferred to HbA1c?", "needed": "Maebashi’s actual population, ingredient, comparator, time point and endpoint, and whether a between-group HbA1c result exists", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish the existence of biotin-only studies from an eligible HbA1c result.", "application_exception": "Do not reclassify observations of low circulating biotin or the long-term combination arm as a sole-biotin comparison treating confirmed deficiency.", "criterion": "Link the originally retained S01 results to the reason for exclusion from direct evidence.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify S01’s actual HbA1c results/plans during an authorized update.", "current_reports": [ "S01" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F01/S01 concern fasting-glucose and circulating-biotin results, not between-group HbA1c results. The original KO did not recast the observed low levels as a trial treating confirmed deficiency.", "condition_status": "Met", "status_reason": "The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time.", "missingness": "The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time.", "uncertainty": "The publisher_full_pdf level reported at the time does not mean an external PDF was read now. Specific numbers are referenced separately in numeric_evidence and were not read this time.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Maebashi’s actual population, ingredient, comparator, time point and endpoint, and whether a between-group HbA1c result exists" }, { "item_id": "N18", "question_type": "Baseline values", "question": "Is Báez-Saldaña’s baseline glycated hemoglobin a follow-up effect?", "needed": "Baseline and follow-up HbA1c; the 28-day comparison; table/analysis definitions", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid misreading baseline characteristics as an estimate of between-group change.", "application_exception": "Do not recast enzyme or metabolic markers as between-group HbA1c follow-up results.", "criterion": "Distinguish S02’s baseline/other results from the unverified eligible effect.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are 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", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify the HbA1c follow-up contrast, denominator and time point in the original results tables.", "current_reports": [ "S02", "S03" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F02/S02/S03 contain baseline glycated hemoglobin and enzyme/other metabolic-marker data; an eligible between-group HbA1c change/endpoint effect was not verified. The evidence field reports a randomized, blinded 28-day protocol after a cross-sectional phase.", "condition_status": "Met", "status_reason": "Verifying a study’s existence and baseline values does not establish a direct follow-up effect.", "missingness": "Verifying a study’s existence and baseline values does not establish a direct follow-up effect.", "uncertainty": "Verifying a study’s existence and baseline values does not establish a direct follow-up effect.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Baseline and follow-up HbA1c; the 28-day comparison; table/analysis definitions" }, { "item_id": "N19", "question_type": "Dose correction", "question": "Were the location-specific values in the µmol/day erratum preserved?", "needed": "Relevant locations in the original text and erratum; the 6.14/61.4/20.5 µmol notations; the relationship between versions", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid creating a new dose by ignoring the erratum or standardizing the values to a single value.", "application_exception": "Do not turn unclear locations or units into arbitrary mg conversions or personal prescriptions.", "criterion": "Link the location-specific correction notations and remaining identity/interpretation limitations to the original text.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify the original bytes, locations and versions of the original text and erratum, and update each exposure record.", "current_reports": [ "S02", "S03" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "KO preserves the correction of 6.14 µmol/day to 61.4 µmol/day at several daily-dose locations and the 20.5 µmol/day notation at another specified location. S02/S03 belong to one study-and-erratum family.", "condition_status": "Partly verified", "status_reason": "The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0.", "missingness": "The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0.", "uncertainty": "The retained erratum summary was read, but the original bytes and each detailed location in the external erratum were not read this time. New conversions/corrections: 0.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Relevant locations in the original text and erratum; the 6.14/61.4/20.5 µmol notations; the relationship between versions" }, { "item_id": "N20", "question_type": "Other endpoints", "question": "Are Revilla-Monsalve’s lipid/glucose results HbA1c?", "needed": "S04’s actual lipid, FPG and insulin results, and eligible between-group HbA1c results", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid substituting changes in other metabolic markers for the selected endpoint.", "application_exception": "Do not establish an endpoint match solely from the 28-day randomized placebo design.", "criterion": "Link the other endpoints in the original record to the reason for exclusion from direct HbA1c evidence.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify S04’s original plan/results tables for the presence of eligible HbA1c.", "current_reports": [ "S04" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F03/S04 is a 28-day randomized, blinded placebo comparison with lipid, fasting-glucose and insulin results. Between-group HbA1c results were not verified in the original material.", "condition_status": "Met", "status_reason": "The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL.", "missingness": "The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL.", "uncertainty": "The current URL is a PubMed bibliographic record/abstract. Do not present historical access, including author text, as current reading of the full text at that URL.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S04’s actual lipid, FPG and insulin results, and eligible between-group HbA1c results" }, { "item_id": "N21", "question_type": "Related add-on therapy", "question": "What were the exposure and off-treatment periods in Devi/Ranjani?", "needed": "Biotin 5 mg 2 times daily for 4 weeks; 2 weeks off; metformin 500 mg/day for 6 weeks in both arms; actual endpoints", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to preserve this candidate added-ingredient comparison without confusing duration and endpoints.", "application_exception": "Do not recast 4 weeks of use as 6 weeks of continuous exposure or HbA1c follow-up.", "criterion": "Link the retained exposure, common treatment and off-treatment period to the verified endpoints.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify administration, discontinuation and the presence of HbA1c at each time point in the original plan/results.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S11 allocated 60 participants, 30 per arm, with metformin 500 mg/day for 6 weeks as common treatment and biotin 5 mg 2 times daily for 4 weeks followed by 2 weeks off. The verified weekly endpoints are FPG/PPG.", "condition_status": "Met", "status_reason": "This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect.", "missingness": "This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect.", "uncertainty": "This verifies preservation of the nominal exposure, not an actual eligible HbA1c result or a sustained long-term effect.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Biotin 5 mg 2 times daily for 4 weeks; 2 weeks off; metformin 500 mg/day for 6 weeks in both arms; actual endpoints" }, { "item_id": "N22", "question_type": "Conflicting information", "question": "Were the completer analyses by arm and the flowchart’s 60 participants both retained?", "needed": "S11 results text/tables: control 28 and biotin 26 participants; flowchart: 60 completers; analysis definitions", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid arbitrarily reconciling the conflicting completion/analysis denominators into the selected HbA1c sample.", "application_exception": "Do not read blood-test Hb as HbA1c. Recalculations of the original numbers/changes to the flowchart: 0.", "criterion": "Preserve conflicting denominators within the same report and the limits on attributing results/endpoints.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the original text, flowchart, corrections and analysis specifications to verify the reason for the denominator discrepancy.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S11’s results text/tables present completer analyses of control 28/biotin 26 participants, while the flowchart shows 60 completers. KO preserves both and explicitly states that Hb was not read as HbA1c.", "condition_status": "Conflicting information", "status_reason": "Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either.", "missingness": "Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either.", "uncertainty": "Who was omitted or which denominator is correct was not resolved within the scope of the original retained material. These counts are not used as the eligible HbA1c analysis n either.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S11 results text/tables: control 28 and biotin 26 participants; flowchart: 60 completers; analysis definitions" }, { "item_id": "N23", "question_type": "Positive and nonsignificant findings", "question": "Are week 4 P=.001 and week 6 P=.087 the same result?", "needed": "S11 FPG endpoint comparison: time point, whether biotin had been stopped, P, and whether the endpoint was HbA1c", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid selecting only the positive time point or treating nonsignificance as equivalence.", "application_exception": "Do not transfer FPG results at different time points to an HbA1c effect or turn nonsignificance into an effect of 0.", "criterion": "Retain the differences in results and exposure at the two time points together with the limits on direct attribution.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M15 §15.3.1–15.3.3; internal application; M03 §3.2.1–3.2.4; details on dose, persistence and effect modification are internally designed", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Separately verify the prespecified plan, between-group estimates/intervals at each time point and the effect of discontinuation.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "In the same S11, the week 4 FPG endpoint comparison has nominal P=.001, and week 6 after discontinuation has P=.087. These are FPG results at different time points, not HbA1c.", "condition_status": "Met", "status_reason": "Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed.", "missingness": "Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed.", "uncertainty": "Nonsignificance does not establish equivalence or an exactly null effect. No new CI/effect calculations were performed.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S11 FPG endpoint comparison: time point, whether biotin had been stopped, P, and whether the endpoint was HbA1c" }, { "item_id": "N24", "question_type": "Positive combination-product finding", "question": "Were 447 participants and P=.03 used as a biotin-only HbA1c result?", "needed": "S05: chromium 600 µg+biotin 2 mg/day for 90 days versus placebo; 447 participants; between-group HbA1c P=.03", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "The positive HbA1c result must be preserved while limiting attribution because another ingredient also changed.", "application_exception": "The same background diabetes treatment does not isolate the incremental effects of chromium/biotin individually.", "criterion": "Link the combination-product results to the reason for exclusion from sole-biotin evidence.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Separately verify an eligible HbA1c comparison in which only biotin differs against the same chromium background.", "current_reports": [ "S05" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "Albarracin S05 reports 447 participants, a combination of chromium 600 µg+biotin 2 mg/day for 90 days versus placebo, and a between-group HbA1c-change P=.03. The positive finding is preserved and is not attributed to biotin alone.", "condition_status": "Met", "status_reason": "The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result.", "missingness": "The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result.", "uncertainty": "The direct sole-biotin effect size, CI and clinical importance cannot be filled in from this combination result.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S05: chromium 600 µg+biotin 2 mg/day for 90 days versus placebo; 447 participants; between-group HbA1c P=.03" }, { "item_id": "N25", "question_type": "Study families and denominators", "question": "Were 348 participants and the active arm’s 226 participants counted as a different study/the total n?", "needed": "S05/S08/S13 and review S12: study families; 348=active 226/placebo 122; overlap relationships", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid double-counting original reports, follow-up reports, registries and reviews as replication trials or participants.", "application_exception": "Do not convert a possibly shared cohort into either confirmed independence or confirmed complete identity.", "criterion": "Distinguish verified families/unconfirmed overlaps and report-specific denominators.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare recruitment, periods and participant links across the relevant reports and registries.", "current_reports": [ "S05", "S08", "S12", "S13" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The related combination report’s 348 participants comprise active 226 and placebo 122 participants; 226 is not used as the total n. F04 conservatively groups possible overlap, and the S12 review is not added to its included studies.", "condition_status": "Partly verified", "status_reason": "The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0.", "missingness": "The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0.", "uncertainty": "The number of unique independent trials/total participants is unconfirmed; new sums/back-calculations: 0.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S05/S08/S13 and review S12: study families; 348=active 226/placebo 122; overlap relationships" }, { "item_id": "N26", "question_type": "Bibliographic candidate", "question": "Were Singer/Geohas’s sample and results verified?", "needed": "S09 original text and results tables; actual study linkage to registry S14; sole/combination composition", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish bibliographic discovery from verification of eligible results.", "application_exception": "Do not establish a confirmed shared family or participant count when the registry-number linkage is provisional.", "criterion": "Identify the verified title/index and the unverified original results/registry linkage.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the S09 original text with the S14 history and actual recruitment/results.", "current_reports": [ "S09", "S14" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S09 is primary_index_only for a chromium-biotin combination pilot report. F05’s S14 registry linkage is provisional, and the exact study-to-report link is unconfirmed.", "condition_status": "Partly verified", "status_reason": "The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0.", "missingness": "The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0.", "uncertainty": "The historical scope did not yield result extraction beyond the retained title/index; new access to the original text this time: 0.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S09 original text and results tables; actual study linkage to registry S14; sole/combination composition" }, { "item_id": "N27", "question_type": "Other populations", "question": "Were type 1 HbA1c candidates transferred to T2D?", "needed": "S10’s actual type1 population, common insulin treatment and extraction level", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid counting human studies in a population different from the question’s population as direct results.", "application_exception": "Do not delete data from other populations or use them as evidence that no human studies exist.", "criterion": "Link S10’s actual population mismatch to the historical access limitations.", "basis": "M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status distinctions are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify direct T2D results separately and retain type1 data for a different question.", "current_reports": [ "S10" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F06/S10 is a biotin add-on-to-insulin study in type 1 diabetes and is not directly attributed to the adult T2D question. The historical PMC full access challenge/partial abstract level is preserved separately.", "condition_status": "Met", "status_reason": "The PMC full text was not read this time, and results in the other population were not deleted.", "missingness": "The PMC full text was not read this time, and results in the other population were not deleted.", "uncertainty": "The PMC full text was not read this time, and results in the other population were not deleted.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S10’s actual type1 population, common insulin treatment and extraction level" }, { "item_id": "N28", "question_type": "Registered sole-biotin arm", "question": "Was GUTERRING excluded solely because its title mentions a combination?", "needed": "NCT05832190’s actual 4 arms, biotin-only arm, population/follow-up HbA1c results and plan", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid omitting a potential biotin-only arm candidate solely on the basis of the title.", "application_exception": "Do not claim that an eligible T2D HbA1c result has been verified solely because a biotin-only arm exists.", "criterion": "Indicate separately the retention of the registry candidate and the lack of verified direct results.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M03 §3.2.1; detailed population criteria are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify the registry body/history, population, actual biotin-only arm results and HbA1c time points.", "current_reports": [ "S15" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F08/S15 is a biotin-only arm candidate in an officially indexed pilot open-label randomized 4-arm design. KO records that it was not excluded solely because of the combination wording in the title, but direct T2D HbA1c results remain unverified.", "condition_status": "Partly verified", "status_reason": "An indexed excerpt/shell does not constitute obtaining the complete registry plan/results.", "missingness": "An indexed excerpt/shell does not constitute obtaining the complete registry plan/results.", "uncertainty": "An indexed excerpt/shell does not constitute obtaining the complete registry plan/results.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "NCT05832190’s actual 4 arms, biotin-only arm, population/follow-up HbA1c results and plan" }, { "item_id": "N29", "question_type": "Review and independent replication", "question": "Is a review counted as an original trial or independent verification?", "needed": "The S12 review’s question, search cutoff, included studies/endpoints and links to original reports", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid counting mixtures of endpoints/ingredients and repeated citations as independent results.", "application_exception": "Do not claim to have read the entire review/numeric files this time.", "criterion": "Distinguish the review’s role and the family/endpoint differences among its included original studies.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Compare the review’s inclusion tables with the original reports’ results and the overlap/sole-ingredient boundaries.", "current_reports": [ "S01", "S02", "S04", "S05", "S08", "S09", "S11", "S12", "S13" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "S12 is a 2022 systematic review/meta-analysis serving as a literature map; the retained location is the HbA1c subsection/refs32–39. KO did not double-count the review, original papers, follow-up reports and registries.", "condition_status": "Partly verified", "status_reason": "What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read.", "missingness": "What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read.", "uncertainty": "What was actually read this time was the stored bibliography and linked KO. The external review’s original text, the original bytes of its inclusion tables and its numbers were not read.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The S12 review’s question, search cutoff, included studies/endpoints and links to original reports" }, { "item_id": "N30", "question_type": "Older material", "question": "Do the discovery and access failure concerning Coggeshall constitute a negative result?", "needed": "S16’s actual original text, population, sole-biotin comparison, HbA1c follow-up and historical failure record", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish a candidate whose original text was not obtained from no effect.", "application_exception": "Do not use metadata_and_failed_full_text to represent a current failed-access action or worldwide study absence.", "criterion": "Separate the retained discovery/historical failure from the current unread status and the lack of verified eligible evidence.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify the relevant original text, population and follow-up results during an authorized update.", "current_reports": [ "S16" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "F09/S16 is at the level of bibliographic discovery of a 1985 report. The population/eligible original between-group HbA1c results were not sufficiently verified, and the historical access_level is metadata_and_failed_full_text.", "condition_status": "Partly verified", "status_reason": "The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result.", "missingness": "The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result.", "uncertainty": "The failure at that time is not a failed access attempt this time. Do not count the candidate as a negative result.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "S16’s actual original text, population, sole-biotin comparison, HbA1c follow-up and historical failure record" }, { "item_id": "N31", "question_type": "Search scope", "question": "Is the lack of verified direct evidence expressed as 0 studies worldwide?", "needed": "The 2026-09-15 original review/search scope, ICTRP failure and scope of this reading of retained material", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish a bounded gate from complete absence of literature.", "application_exception": "The 0 searches this time do not mean 0 studies. Historical selection_log/ZIP references do not constitute current acquisition.", "criterion": "Link every expression of absence or lack of verification to its actual scope and date.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify search records, unpublished studies/registries and correction coverage in an authorized update as a separate event.", "current_reports": [ "S13", "S14", "S15", "S16", "S17" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The original KO/assessment limits its statement to not having verified directly eligible results within the documented search scope. S17 WHO ICTRP was internal error/access_failed at the time; current external lookups/searches: 0.", "condition_status": "Met", "status_reason": "Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date.", "missingness": "Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date.", "uncertainty": "Do not retroactively treat the original verified_date/evidence reference date, 9/15, as the current full-text reading date.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "The 2026-09-15 original review/search scope, ICTRP failure and scope of this reading of retained material" }, { "item_id": "N32", "question_type": "Assay interference", "question": "Was TSH/troponin interference generalized to interference with HbA1c itself?", "needed": "NIH/FDA’s specific assays, populations, exposures and time points, with separate verification of the HbA1c assay", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to avoid turning biotin interference into actual glycemic improvement or a risk for every test.", "application_exception": "Statements concerning specific TSH/NT-proBNP/troponin tests do not directly establish interference with an HbA1c assay.", "criterion": "Separate the assay/exposure scope of the retained safety material from the lack of verification for the selected HbA1c endpoint.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.2 design-specific harm questions; temporal-relationship details are internally designed; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Separately verify validation for each relevant HbA1c method and data on biotin exposure/blood-sampling time points.", "current_reports": [ "S06", "S07" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The retained NIH/FDA content concerns selected thyroid tests after a single 10 mg dose within 24 hours, selected TSH/NT-proBNP tests in 6 people receiving 10 mg/day for 1 week, and falsely low results in some troponin tests. It does not establish the same interference in every test/HbA1c method.", "condition_status": "Partly verified", "status_reason": "Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules.", "missingness": "Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules.", "uncertainty": "Do not present the original official extract as actual access to the official full text this time. Do not provide personal dosing, stopping or testing schedules.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "NIH/FDA’s specific assays, populations, exposures and time points, with separate verification of the HbA1c assay" }, { "item_id": "N33", "question_type": "Related adverse events", "question": "Are the frequencies of nausea, loose stools and gastric irritation in S11 known?", "needed": "People with AE/events by arm; collection; exposure/follow-up; safety-analysis denominators; discontinuation", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Needed to distinguish the presence of symptoms from incidence rates or a guarantee of long-term safety.", "application_exception": "Do not calculate event rates or NNH from unclear safety denominators, or treat unreported data as 0.", "criterion": "Link the retained symptoms to gaps in safety denominators/directly eligible exposure.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Separately verify the original AE tables, collection methods and arm-specific denominators/discontinuations.", "current_reports": [ "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "KO preserves nausea, loose stools and gastric irritation from the trial with common metformin treatment and states that the safety-analysis denominator is unclear. The stored summary read this time retains a reference to numeric_evidence N12 instead of specific event counts.", "condition_status": "Partly verified", "status_reason": "The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy.", "missingness": "The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy.", "uncertainty": "The numeric file and original safety tables were not read this time. Do not elevate limited short-term experience involving another endpoint into long-term safety of sole-biotin add-on therapy.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "People with AE/events by arm; collection; exposure/follow-up; safety-analysis denominators; discontinuation" }, { "item_id": "N34", "question_type": "Long-term use and vulnerable groups", "question": "Is there safety evidence for long-term use, pregnancy/lactation, children, hepatic/renal disease and concurrent use?", "needed": "Long-term AE and discontinuations by eligible dose; population-specific exposure/interactions and denominators", "role": "Supplementary; required for the corresponding extended claims about long-term or special-population safety", "role_reason": "Needed to avoid guaranteeing safety in all populations from some brief observations.", "application_exception": "Do not unconditionally require every rare-harm study for the current narrow HbA1c question.", "criterion": "Distinguish direct information in the same population/exposure from unverified extensions.", "basis": "M19 §19.1.2–19.2.4; internal application; Chamgap’s own interpretation boundaries. M19 principles are referenced; no formal causality tool was applied", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Separately verify long-term/population-specific harms and observation conditions for the same product and dose.", "current_reports": [ "S06", "S07", "S11" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The original safety_detail explicitly states that long-term add-on use in T2D, pregnancy, lactation, children, hepatic/renal disease, concurrent use and eligible dose-specific AE/discontinuations are unverified.", "condition_status": "Unverified", "status_reason": "Unverified information does not establish either safety or harm, and no personal dosing instructions are created.", "missingness": "Unverified information does not establish either safety or harm, and no personal dosing instructions are created.", "uncertainty": "Unverified information does not establish either safety or harm, and no personal dosing instructions are created.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Long-term AE and discontinuations by eligible dose; population-specific exposure/interactions and denominators" }, { "item_id": "N35", "question_type": "Independence and funding", "question": "Is the actual scope of funding, product provision and COI known?", "needed": "Report-specific funding, product provision, author relationships, COI declarations and original verification locations", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Required to avoid treating unverified funding as absent or as certification of independence.", "application_exception": "Do not automatically exclude a study or judge it free of bias solely on historical wording stating the presence or absence of COI.", "criterion": "Distinguish the level of disclosures/funding actually verified from materials not read in this review.", "basis": "Chamgap’s own independence and attribution criteria. The official methodological sections used in this pilot do not warrant all these detailed items; the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is an internal application.", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Verify original research funding/COI and product supply records by report.", "current_reports": [ "S01", "S02", "S04", "S05", "S08", "S09", "S10", "S11", "S15", "S16" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The funding fields of the 9 evidence items refer to trial_families.json for detailed verified and unverified information. The S11 location includes p106 COI, but the currently retained summary does not reproduce the specific disclosures.", "condition_status": "Unverified", "status_reason": "The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement.", "missingness": "The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement.", "uncertainty": "The existence of a referenced file or COI location does not mean its contents were read in this review. Do not infer the number of independent trials or lack of industry involvement.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Report-specific funding, product provision, author relationships, COI declarations and original verification locations" }, { "item_id": "N36", "question_type": "Reading level", "question": "Have historical full-text access and current summary reading been separated?", "needed": "Historical access_level/location by report; actual access dates; current local locations/values/SHA; external access unattempted", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Required to avoid retroactively treating retained statements of PDF access as full-text reading in this review.", "application_exception": "If a report has no date field, leave it null; the global verified_date is a separate review date.", "criterion": "Link reading badges to the actual retained citations and keep unread external materials separate.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "If new access is separately authorized, independently record the material/time/original bytes.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12", "S13", "S14", "S15", "S16", "S17" ], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "What was actually read in this review consists of the exact retained Korean content, bibliography and structure/metadata, with the retained summaries’ locations/values/SHA. publisher_full_pdf, author_text, official_extract, shell and failure are historical records; external materials/referenced historical ZIP files have not been read in this review.", "condition_status": "Met", "status_reason": "Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition.", "missingness": "Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition.", "uncertainty": "Each report’s historical access date is null because the source material contains no date; retain the review date 9/15 in a separate field. The existence of an external URL is not new acquisition.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Historical access_level/location by report; actual access dates; current local locations/values/SHA; external access unattempted" }, { "item_id": "N37", "question_type": "Original gate and score", "question": "Have ?/null values and no_human_study=true been preserved unchanged?", "needed": "Original ?/null score; B/S; nulls on the subsequent 5 axes; bounded human scope; related studies true", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Required to avoid treating the historical calculator gate as absence of all human studies or as a new efficacy grade.", "application_exception": "Do not alter the original false/true/null values for convenience or convert them to a score of 0 or a new criterion-fulfillment rate.", "criterion": "Separate the scope expressed by the original verdict/gate from the statuses of the new criteria.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.5, §4.6.3; the limits of the current data conversion follow the user’s scope and internal design; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "If direct evidence is added, consider a separate update that preserves the original values/reasons for change.", "current_reports": [], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "Preserve the original ?, null score, B/S, nulls on the subsequent 5 axes, no_human_study=true and human_study_exists=false unchanged. The assessment’s scope is direct eligible HbA1c results, and related_human_studies_exist=true.", "condition_status": "Met", "status_reason": "Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict.", "missingness": "Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict.", "uncertainty": "Blue in this table indicates verification of the stated preservation/boundary criteria; it does not establish a direct effect, constitute official methodological certification or represent a new verdict.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original ?/null score; B/S; nulls on the subsequent 5 axes; bounded human scope; related studies true" }, { "item_id": "N38", "question_type": "Technical and deployment metadata", "question": "Have server_deployed and actual deployment in this work been distinguished?", "needed": "Original server_deployed/server_write_performed/first_published_scope; current local preparation", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Required to avoid treating historical deployment metadata as evidence of site publication in this work.", "application_exception": "Do not arbitrarily reconcile the original server_deployed=true and server_write=false.", "criterion": "Separate the original metadata values/scope from the current local conversion and absence of public deployment.", "basis": "M04 §4.5–4.6 data collection/selection principles; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current data conversion derive from the user-defined scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "If actual publication is separately authorized, verify the production URL/display/links and record the event.", "current_reports": [], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "Preserve the original server_deployed=true, server_write_performed=false, deployed_at 2026-09-15 and initial snapshot scope. This work is a local table conversion, with 0 public site deployments.", "condition_status": "Met", "status_reason": "Do not certify the current actual publication status solely from the original metadata.", "missingness": "Do not certify the current actual publication status solely from the original metadata.", "uncertainty": "Do not certify the current actual publication status solely from the original metadata.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original server_deployed/server_write_performed/first_published_scope; current local preparation" }, { "item_id": "N39", "question_type": "Boundaries for extensions", "question": "Does the HbA1c table also answer questions about clinical events and improvements in quality of life?", "needed": "Boundary between the selected HbA1c question and separate questions about complications, quality of life, mortality, duration/dose", "role": "Supplementary; required for extended claims about clinical events, duration and dose", "role_reason": "Required to avoid extending a numerical surrogate outcome to benefits in clinical events.", "application_exception": "Do not make clinical-event trials an unconditional requirement for the numerical HbA1c question.", "criterion": "Separate the directly selected endpoint from additional questions extending beyond it.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adapting outcomes to each question is internally designed; M03 §3.2.1–3.2.4; details concerning dose, duration and effect modification are internally designed; M03 §3.2.4; internal boundaries for extensions", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Review direct results and criteria separately for questions about events/long-term outcomes/dose.", "current_reports": [], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The selected question concerns between-group numerical HbA1c results. The original assessment uses an S surrogate and does not upgrade it to an H clinical event/P functional endpoint.", "condition_status": "Not applicable", "status_reason": "The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits.", "missingness": "The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits.", "uncertainty": "The criterion is not applicable because event studies are not required to complete this numerical table; this does not substitute for verification or nonverification of clinical-event benefits.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Boundary between the selected HbA1c question and separate questions about complications, quality of life, mortality, duration/dose" }, { "item_id": "N40", "question_type": "Updating and tracking", "question": "What changes when new direct results, full texts or corrections are acquired?", "needed": "Original identity/dates; original values before/after; corrections/retractions; criterion versions; update links", "role": "Required (selected sole-added-biotin/HbA1c comparison)", "role_reason": "Required to avoid making the current table a fixed truth or an automatic efficacy upgrade.", "application_exception": "Adding new materials is separate from amending criteria/reaching a new verdict and from deployment; do not exceed the current authorized scope.", "criterion": "Explicitly link update triggers, required materials and affected items/preservation of history.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed; M04 §4.5, §4.6.3; the limits of the current data conversion follow the user’s scope and internal design", "condition_origin": "Disclosed development conditions designed after reading the current 3105 retained materials; not blinded, clinically preregistered or independently clinically certified", "proposed_research": "Register separately authorized full texts, direct HbA1c results and corrections with their exact locations/values/hashes, then review the linked items again.", "current_reports": [], "existence": "Current stored bibliographic/structural and historical records exist; this is not an up-to-date external check of existence or corrections", "acquired_read": "Exactly preserved stored summaries: summary locations/values actually read; external full texts and older separate reference files not read in this review", "observation": "The original revision_triggers are new direct HbA1c results, full texts/registrations/SAPs, corrections/retractions, numerical/classification errors and new safety materials. Maintain the same ID/URL and the policy of retaining old/new/reason/source/date.", "condition_status": "Met", "status_reason": "No new search, calculation, update to the original verdict or public release was performed in this work.", "missingness": "No new search, calculation, update to the original verdict or public release was performed in this work.", "uncertainty": "No new search, calculation, update to the original verdict or public release was performed in this work.", "review_date": "2026-10-05", "reading_status": "Original source not read · Stored summary read", "additional_material": "Original identity/dates; original values before/after; corrections/retractions; criterion versions; update links" } ], "reports": [ { "report_id": "S01", "title": "Maebashi et al. 1993. Therapeutic Evaluation of the Effect of Biotin on Hyperglycemia in Patients with Non-Insulin Dependent Diabetes Mellitus", "url": "https://www.jstage.jst.go.jp/article/jcbn1986/14/3/14_3_211/_pdf", "report_type": "Reports on biotin alone and other endpoints", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F01", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "S01 fasting-glucose/blood-biotin data; direct between-group HbA1c result unverified", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: J Clin Biochem Nutr 14:211–218; Methods pp212–213; results p214; whole-paper endpoint inspection. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S01-M1", "url": null, "bibliographic_url": null }, { "material_type": "Publisher PDF link", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: J Clin Biochem Nutr 14:211–218; Methods pp212–213; results p214; whole-paper endpoint inspection. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S01-M2", "url": "https://www.jstage.jst.go.jp/article/jcbn1986/14/3/14_3_211/_pdf", "bibliographic_url": "https://www.jstage.jst.go.jp/article/jcbn1986/14/3/14_3_211/_pdf" } ], "links": [ { "label": "Source", "url": "https://www.jstage.jst.go.jp/article/jcbn1986/14/3/14_3_211/_pdf" } ] }, { "report_id": "S02", "title": "Báez-Saldaña et al. 2004. Effects of biotin on carboxylases and markers for glucose and lipid homeostasis", "url": "https://www.researchgate.net/publication/7754969_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects", "report_type": "Original report on biotin alone", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F02", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "S02 baseline glycated hemoglobin and enzyme/metabolic markers; follow-up between-group HbA1c result unverified", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: author_uploaded_full_text. Historically recorded location: Am J Clin Nutr 79:238–243; p239 procedures; Table2 p241; discussion p242; baseline characteristics. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S02-M1", "url": null, "bibliographic_url": null }, { "material_type": "Author-shared full-text page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: author_uploaded_full_text. Historically recorded location: Am J Clin Nutr 79:238–243; p239 procedures; Table2 p241; discussion p242; baseline characteristics. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S02-M2", "url": "https://www.researchgate.net/publication/7754969_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects", "bibliographic_url": "https://www.researchgate.net/publication/7754969_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/7754969_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects" } ] }, { "report_id": "S03", "title": "Báez-Saldaña et al. 2007. Erratum to 2004 biotin study", "url": "https://www.researchgate.net/publication/297184582_Erratum_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects_Am", "report_type": "S02 dose erratum", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F02", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Preserve location-specific 6.14→61.4 µmol/day and 20.5 µmol/day at other specified locations; new conversions: 0", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: author_uploaded_correction_text. Historically recorded location: Am J Clin Nutr 85:570; correction paragraph. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S03-M1", "url": null, "bibliographic_url": null }, { "material_type": "Author-shared correction page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: author_uploaded_correction_text. Historically recorded location: Am J Clin Nutr 85:570; correction paragraph. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S03-M2", "url": "https://www.researchgate.net/publication/297184582_Erratum_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects_Am", "bibliographic_url": "https://www.researchgate.net/publication/297184582_Erratum_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects_Am" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/297184582_Erratum_Effects_of_biotin_on_pyruvate_carboxylase_acetyl-CoA_carboxylase_propionyl-CoA_carboxylase_and_markers_for_glucose_and_lipid_homeostasis_in_type_2_diabetic_patients_and_nondiabetic_subjects_Am" } ] }, { "report_id": "S04", "title": "Revilla-Monsalve et al. 2006. Biotin supplementation reduces plasma triacylglycerol and VLDL", "url": "https://pubmed.ncbi.nlm.nih.gov/16677798/", "report_type": "Reports on biotin alone and other endpoints", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F03", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Lipids, FPG and insulin; eligible between-group HbA1c result unverified", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_and_author_text. Historically recorded location: Biomed Pharmacother 60:182–185; abstract; Methods subjects/treatment and outcome table. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S04-M1", "url": null, "bibliographic_url": null }, { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. S04’s historical access to the author’s text does not mean current full-text reading at this PubMed URL. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_and_author_text. Historically recorded location: Biomed Pharmacother 60:182–185; abstract; Methods subjects/treatment and outcome table. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S04-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/16677798/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/16677798/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/16677798/" } ] }, { "report_id": "S05", "title": "Albarracin et al. 2008. Chromium picolinate and biotin combination improves glucose metabolism", "url": "https://pubmed.ncbi.nlm.nih.gov/17506119/", "report_type": "Chromium–biotin combination HbA1c report", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F04", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "447 participants, 90 days; chromium 600µg+biotin 2mg/P=.03; not attributable to biotin alone", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: pubmed_primary_abstract. Historically recorded location: Diabetes Metab Res Rev 24:41–51; abstract Methods/Results. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S05-M1", "url": null, "bibliographic_url": null }, { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: pubmed_primary_abstract. Historically recorded location: Diabetes Metab Res Rev 24:41–51; abstract Methods/Results. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S05-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/17506119/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/17506119/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/17506119/" } ] }, { "report_id": "S06", "title": "NIH Office of Dietary Supplements: Biotin—Health Professional Fact Sheet", "url": "https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/", "report_type": "Official NIH safety materials", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "Official_safety_explanation", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Biotin interference under specific assay and exposure conditions; does not demonstrate interference with HbA1c itself or all tests", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S06-M1", "url": null, "bibliographic_url": null }, { "material_type": "Official NIH ODS web document", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S06-M2", "url": "https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/", "bibliographic_url": "https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/" } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/" } ] }, { "report_id": "S07", "title": "FDA: Biotin Interference with Troponin Lab Tests—Assays Subject to Biotin Interference", "url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference", "report_type": "FDA troponin assay safety materials", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "Official_safety_explanation", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Falsely low results in some troponin assays; not direct evidence of actual HbA1c efficacy/risk rates", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Opening safety statement and paragraphs on residual assay interference. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S07-M1", "url": null, "bibliographic_url": null }, { "material_type": "Official FDA web document", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: inherited_official_extract. Historically recorded location: Opening safety statement and paragraphs on residual assay interference. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S07-M2", "url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference", "bibliographic_url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference" } ], "links": [ { "label": "Source", "url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference" } ] }, { "report_id": "S08", "title": "Albarracin et al. 2007. Chromium and biotin: coronary risk factors in type 2 diabetes", "url": "https://pubmed.ncbi.nlm.nih.gov/17684468/", "report_type": "Related follow-up report on the combination", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F04_possible_overlap", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "348 participants, active 226/placebo 122; possible shared cohorts conservatively grouped/independent summations: 0", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_mirror. Historically recorded location: J Cardiometab Syndr 2:91–97; abstract N=348, active226/placebo122. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S08-M1", "url": null, "bibliographic_url": null }, { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_mirror. Historically recorded location: J Cardiometab Syndr 2:91–97; abstract N=348, active226/placebo122. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S08-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/17684468/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/17684468/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/17684468/" } ] }, { "report_id": "S09", "title": "Singer and Geohas 2006. Chromium picolinate and biotin supplementation in poorly controlled type 2 diabetes", "url": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "report_type": "Bibliographic candidate for a combination pilot", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F05_provisional_registry_link", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Original outcome extraction not acquired; S14 linkage provisional; not direct data on HbA1c from biotin alone", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_index_only. Historically recorded location: Title and bibliographic record; full outcome extraction not obtained. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S09-M1", "url": null, "bibliographic_url": null }, { "material_type": "PubMed bibliographic record and abstract", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_index_only. Historically recorded location: Title and bibliographic record; full outcome extraction not obtained. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S09-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/17109595/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/17109595/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/17109595/" } ] }, { "report_id": "S10", "title": "Hemmati et al. 2013. Survey of biotin, glycemic control and plasma lipids in type 1 diabetes", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3679599/", "report_type": "Report in a different population: type 1 diabetes", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F06", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Type 1 insulin add-on data; excluded from the direct T2D question/historical partial PMC access", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: primary_abstract_index_partial. Historically recorded location: Title/abstract population; full PMC access challenge. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S10-M1", "url": null, "bibliographic_url": null }, { "material_type": "PMC full-text page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: primary_abstract_index_partial. Historically recorded location: Title/abstract population; full PMC access challenge. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S10-M2", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3679599/", "bibliographic_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3679599/" } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3679599/" } ] }, { "report_id": "S11", "title": "Devi and Ranjani 2016. Biotin added to metformin versus metformin alone in newly diagnosed type 2 diabetes", "url": "https://www.iosrjournals.org/iosr-jdms/papers/Vol15-Issue%207/Version-9/R1507910106.pdf", "report_type": "Sole added active ingredient: FPG/PPG report", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F07", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Common metformin allowed; HbA1c unverified; completers 28/26 versus flowchart 60; FPG P values at 4/6 weeks preserved", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: IOSR-JDMS 15(7)IX:100–106; p101 methods/flowchart; p102 completers/Table4; p104 Tables6–7; p105 Tables8–9; p106 COI. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S11-M1", "url": null, "bibliographic_url": null }, { "material_type": "Publisher PDF link", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_pdf. Historically recorded location: IOSR-JDMS 15(7)IX:100–106; p101 methods/flowchart; p102 completers/Table4; p104 Tables6–7; p105 Tables8–9; p106 COI. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S11-M2", "url": "https://www.iosrjournals.org/iosr-jdms/papers/Vol15-Issue%207/Version-9/R1507910106.pdf", "bibliographic_url": "https://www.iosrjournals.org/iosr-jdms/papers/Vol15-Issue%207/Version-9/R1507910106.pdf" } ], "links": [ { "label": "Source", "url": "https://www.iosrjournals.org/iosr-jdms/papers/Vol15-Issue%207/Version-9/R1507910106.pdf" } ] }, { "report_id": "S12", "title": "Zhang et al. 2022. Biotin interventions in type 2 diabetes: systematic review and meta-analysis", "url": "https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1046800/full", "report_type": "Systematic review/meta-analysis", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "Review_literature_map", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Included studies, combinations/sole ingredients and endpoints must be distinguished; duplicate summations as independent trials: 0", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: publisher_full_text. Historically recorded location: Methods/search cutoff; HbA1c subsection; references32–39. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S12-M1", "url": null, "bibliographic_url": null }, { "material_type": "Publisher’s review full-text page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: publisher_full_text. Historically recorded location: Methods/search cutoff; HbA1c subsection; references32–39. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S12-M2", "url": "https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1046800/full", "bibliographic_url": "https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1046800/full" } ], "links": [ { "label": "Source", "url": "https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.1046800/full" } ] }, { "report_id": "S13", "title": "ClinicalTrials.gov NCT00289354", "url": "https://clinicaltrials.gov/study/NCT00289354", "report_type": "NCT00289354 registry record", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F04_registry_shell", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Registry URL/shell for the combination family; not upgraded to verification of the body text or plan", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL verified, rendered body not available. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S13-M1", "url": null, "bibliographic_url": null }, { "material_type": "ClinicalTrials.gov registry page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL verified, rendered body not available. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S13-M2", "url": "https://clinicaltrials.gov/study/NCT00289354", "bibliographic_url": "https://clinicaltrials.gov/study/NCT00289354" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT00289354" } ] }, { "report_id": "S14", "title": "ClinicalTrials.gov NCT00308451", "url": "https://clinicaltrials.gov/study/NCT00308451", "report_type": "NCT00308451 registry record", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F05_provisional_registry_link", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Shell only; exact report linkage unconfirmed; not counted as a new independent study", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL accessed; exact study-to-report link not established. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S14-M1", "url": null, "bibliographic_url": null }, { "material_type": "ClinicalTrials.gov registry page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_shell_only. Historically recorded location: Record URL accessed; exact study-to-report link not established. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S14-M2", "url": "https://clinicaltrials.gov/study/NCT00308451", "bibliographic_url": "https://clinicaltrials.gov/study/NCT00308451" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT00308451" } ] }, { "report_id": "S15", "title": "ClinicalTrials.gov NCT05832190: GUTERRING", "url": "https://clinicaltrials.gov/study/NCT05832190", "report_type": "GUTERRING registry candidate", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F08", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "4-arm/biotin-only-arm candidate retained; eligible T2D HbA1c results/body text unverified", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: registry_search_excerpt_and_shell. Historically recorded location: Official indexed title/design excerpt; direct body unavailable. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S15-M1", "url": null, "bibliographic_url": null }, { "material_type": "ClinicalTrials.gov registry page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: registry_search_excerpt_and_shell. Historically recorded location: Official indexed title/design excerpt; direct body unavailable. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S15-M2", "url": "https://clinicaltrials.gov/study/NCT05832190", "bibliographic_url": "https://clinicaltrials.gov/study/NCT05832190" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT05832190" } ] }, { "report_id": "S16", "title": "Coggeshall et al. 1985. Biotin Status and Plasma Glucose in Diabetics", "url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1985.tb18454.x", "report_type": "Older bibliographic record; full text not acquired", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "F09", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "1985 full text/eligible population/between-group HbA1c details unverified; the failure at the time was not a negative result", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: metadata_and_failed_full_text. Historically recorded location: Ann NY Acad Sci 447:389–392; article identified, outcome detail inaccessible. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S16-M1", "url": null, "bibliographic_url": null }, { "material_type": "Publisher’s article page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: metadata_and_failed_full_text. Historically recorded location: Ann NY Acad Sci 447:389–392; article identified, outcome detail inaccessible. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S16-M2", "url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1985.tb18454.x", "bibliographic_url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1985.tb18454.x" } ], "links": [ { "label": "Source", "url": "https://nyaspubs.onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.1985.tb18454.x" } ] }, { "report_id": "S17", "title": "WHO ICTRP portal search for biotin", "url": "https://trialsearch.who.int/?query=biotin", "report_type": "WHO ICTRP search record", "existence": "References to retained bibliographic and historical records; current external responses have not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original sources have not been read in this review.", "study_family": "Search_historical_failure", "independent_replication": "17 bibliographic records ≠ 17 independent trials. Distinguish studies/corrections, possible duplicates/registrations, reviews/official safety sources/search roles; new summations of trials/participants: 0", "observed_result": "Historical internal error/access_failed; not an outcome or evidence of 0 studies worldwide", "result_level": "Information recorded in the retained manuscript. It is not the result of a new comparison against external original sources in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived summary: bibliography, linked summary/historical access", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-05", "qualification": "Exact retained-summary location/value/SHA, not the original bytes of the clinical full text. What was read in this review consists of the retained report summaries and bibliographic records. This does not mean that the original bytes of external clinical full texts were acquired. Historical access level recorded for the report: access_failed. Historically recorded location: Search endpoint attempted, returned internal error. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S17-M1", "url": null, "bibliographic_url": null }, { "material_type": "WHO ICTRP search page", "public_status": "Unverified (0 external lookups in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Indicates the physical material type of the link target. Distinguishes historical access from access not attempted and materials not read in this review. No attempt was made to access this external material or read its full text in this review. What was read consists of the retained report summaries. Historical access level recorded for the report: access_failed. Historically recorded location: Search endpoint attempted, returned internal error. Historical report-level access is not inherited as the material’s current reading status. The actual historical access date is unverified, and the retained manuscript’s review date 2026-09-15 is not an access date for the original source.", "material_id": "S17-M2", "url": "https://trialsearch.who.int/?query=biotin", "bibliographic_url": "https://trialsearch.who.int/?query=biotin" } ], "links": [ { "label": "Source", "url": "https://trialsearch.who.int/?query=biotin" } ] } ], "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": "Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool 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": "Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool 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": "Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool 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": "Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool 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": "Method principles/editions from 1585 and actual byte-for-byte copies of 5 HTML files reused; no new reading of full methodological texts or execution of an official tool in this work" } ], "status_dictionary": { "Partly verified": "Some related materials/identity/historical information are available, but gaps remain in direct comparisons, plans, access and harms", "Unverified": "The actual materials required for the selected direct comparison could not be verified within the retained scope; this does not mean no effect or 0 studies", "Review incomplete": "Comparison against original sources/search was not performed within the authorized scope", "Not reported": "A scoped status indicating that the item is not stated in the specific material/section that was read", "Inaccessible": "Used only for materials for which access was actually attempted and failed. Not assigned to the clinical materials in this work", "Insufficient evidence for this criterion": "Used only when relevant studies within a defined scope have been reviewed and the evidence is insufficient to answer the criterion. Not applied to all items in this work", "Not applicable": "The extension requiring clinical events beyond HbA1c does not apply; not a substitute for Unverified", "Conflicting information": "The conflict between completer and flowchart denominators in the same report is preserved; no new calculation or correction", "Met": "Verification of the stated preservation/boundary, distinction and linkage criteria; not new direct HbA1c efficacy evidence, full-text reading or safety certification" }, "study_overlap": { "state": "These are report linkages from the original material. The 17 citations, 9 retained evidence items and 10 family links are different structural counts, not the number of independent eligible direct clinical trials. S01: F01: excluded from direct efficacy scoring / S02, S03: F02: excluded from direct efficacy scoring / S04: F03: excluded from direct efficacy scoring / S05, S08, S13: F04: excluded from direct efficacy scoring / S09, S14: F05: excluded from direct efficacy scoring / S10: F06: excluded from direct efficacy scoring / S11: F07: excluded from direct efficacy scoring / S15: F08: excluded from direct efficacy scoring / S16: F09: excluded from direct efficacy scoring / S06, S07, S12, S17: official safety sources, review literature map and historical search failure; not counted as independent direct HbA1c trials. Original reports, corrections, follow-up reports, registrations and reviews are not added as independent replications. Possible shared cohorts and provisional registry links are retained; unique trial and total participant counts remain unverified.", "unique_trial_count": null, "unique_participant_count": null, "reason": "These are report linkages from the original material. The 17 citations, 9 retained evidence items and 10 family links are different structural counts, not the number of independent eligible direct clinical trials. S01: F01: excluded from direct efficacy scoring / S02, S03: F02: excluded from direct efficacy scoring / S04: F03: excluded from direct efficacy scoring / S05, S08, S13: F04: excluded from direct efficacy scoring / S09, S14: F05: excluded from direct efficacy scoring / S10: F06: excluded from direct efficacy scoring / S11: F07: excluded from direct efficacy scoring / S15: F08: excluded from direct efficacy scoring / S16: F09: excluded from direct efficacy scoring / S06, S07, S12, S17: official safety sources, review literature map and historical search failure; not counted as independent direct HbA1c trials. Original reports, corrections, follow-up reports, registrations and reviews are not added as independent replications. Possible shared cohorts and provisional registry links are retained; unique trial and total participant counts remain unverified." }, "history": [ { "date": "2026-11-03", "kind": "Separation of public-facing display and data", "view_version": "1.0", "change": "Public-facing display and data were created from the existing 40 items. No new clinical search, change in verification status or scoring was performed." } ], "language": "en", "translation_date": "2026-11-03" }