{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3104-main", "verdict_number": "3104", "title": "Biotin (vitamin B7), sole-active oral product × Reduction of recurrent brittle-nail breakage events over a standardized observation period", "view_version": "1.0", "view_created_date": "2026-11-03", "criteria_version": "NGM-v3104-BIOTIN-RECURRENT-NAIL-BREAKAGE-1.2", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Retained Korean and English manuscripts and case-specific condition 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 retained summaries read in this review. The original verdict, numbers, and unverified matters have been preserved; no new search, calculation, or reassessment was performed.", "date_meaning": "This is the date the retained materials were reviewed, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Adults with general brittle nails, with separate fingernail and toenail strata; confirmed deficiency correction and specific secondary causes excluded; unreported biotin status not presumed normal", "intervention": "Biotin (biotin, vitamin B7), sole active ingredient · The question is bounded to a sole-active oral product; tablet or capsule, excipients, batch, and purity unverified · Oral; topical use, injection, and effects of topical products themselves excluded", "dose": "Unverified — eligible regimen dose, dosing frequency, and total dietary and concurrent supplement intake", "comparator": "Placebo, no-treatment, and usual-care comparisons with the same background conditions are each preserved; the actual eligible comparator is unverified", "endpoint": "Between-group change difference or difference in event counts over the same prespecified period; event rates treated separately when exposure time is verified; distinguished from thickness, hardness, PGA, and OGSS", "duration": "Unverified — the actual treatment duration and the prespecified breakage observation period each require verification", "excluded_extensions": "Confirmed deficiency correction and specific secondary causes; topical use, injection, and effects of topical products themselves; products with multiple or other active ingredients; and thickness, growth, hardness, surface, photographs, PGA, OGSS, and satisfaction are excluded from this recurrent breakage-event question. Fingernails and toenails are not pooled, and comparisons of biotin added to the same topical care are distinguished as conditional add-on effects." }, "requirements": [ { "item_id": "N01", "question_type": "Independent question boundary", "question": "Does this table address a single question about recurrent breakage events per person with oral biotin alone?", "needed": "Exact original wording of the current claim, population, ingredient, route, comparator, and recurrent-event endpoint", "role": "Required", "role_reason": "Needed to avoid combining improved thickness or hardness and reduced breakage counts as the same efficacy outcome.", "application_exception": "Fingernails and toenails remain separate strata. The fact that direct results are currently unverified does not by itself justify creating a new, separate completed table for each stratum.", "criterion": "Link the same question as in the original /ko/effect and specify event counts per person over a prespecified period and the excluded endpoints.", "basis": "M03 §3.1, §3.2.1–3.2.4 question-clarification principles; detailed separation rules are internally designed; M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.4; internally designed extension boundary", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "In a comparative study with a fixed question, prespecify the event definition and observation period and separate estimates by site.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original claim is a reduction in brittle-nail breakage-event frequency over a standardized observation period. The table selects the between-group recurrent-event-count question for oral biotin as the sole active ingredient and separates thickness, growth, hardness, PGA, OGSS, and satisfaction.", "condition_status": "Met", "status_reason": "The currently retained original claim, crux, and facets specify the same selected question. This verifies the identity of the question, not an actual effect.", "missingness": "Directly eligible breakage-event results, measurement definitions, periods, and effect values remain unverified.", "uncertainty": "Directly eligible breakage-event results, measurement definitions, periods, and effect values remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Exact original wording of the current claim, population, ingredient, route, comparator, and recurrent-event endpoint" }, { "item_id": "N02", "question_type": "Sole active ingredient", "question": "Is biotin the only additional active ingredient in the actual study product?", "needed": "Original text on product composition, active ingredients, background treatment, and batch by arm", "role": "Required", "role_reason": "Needed to avoid attributing the effects of other active ingredients in a biotin-labeled product to biotin alone.", "application_exception": "If both arms receive the same background topical product, retain the comparison as a candidate for the add-on effect of biotin. Do not recast a plant extract itself as pure biotin.", "criterion": "Indicate the sole-active question and the differences between actual products with a sole active ingredient, combinations, and a common background treatment.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Design a comparison that keeps active ingredients other than biotin and background care identical, and disclose product composition.", "current_reports": [ "S24", "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The question concerns oral biotin alone. Chiavetta compares biotin added to the same lacquer, but the endpoint differs. Patel's biotin-labeled arm uses Sesbania extract, and a sole-active-ingredient effect was not isolated.", "condition_status": "Partly verified", "status_reason": "The common lacquer and plant-extract differences in the actual materials were verified, but a product in an eligible recurrent-event comparison was not verified.", "missingness": "The eligible formulation's composition, chemical form, purity, batch, and the contribution of biotin alone are unverified.", "uncertainty": "The eligible formulation's composition, chemical form, purity, batch, and the contribution of biotin alone are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original text on product composition, active ingredients, background treatment, and batch by arm" }, { "item_id": "N03", "question_type": "Formulation identity", "question": "Was an eligible sole-active product used whose chemical form, source, tablet/capsule form, excipients, and batch were verified?", "needed": "Chemical form, manufacturing source, dosage form, excipients, and batch/purity records for the eligible product", "role": "Required", "role_reason": "Needed to avoid concealing an unverified product identity behind an assumption that the biotin formulations are identical.", "application_exception": "The word biotin in a bibliographic title does not establish the exact chemical form or purity. Do not invent an unknown brand to fill the gap.", "criterion": "Link only verified product identity information and preserve the null values in actual_trial_fields.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Obtain quantitative content, purity, and dosage-form data for the same batch in a comparative study, and track differences other than the active ingredient.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The chemical form, source, tablet/capsule form, excipients, batch, and purity of the current eligible formulation are all retained as not_verified with null values.", "condition_status": "Unverified", "status_reason": "The question's sole-active-product boundary is known, but identity data for an actual formulation with direct event results are unavailable.", "missingness": "Actual analytical and batch information for the eligible product is unverified.", "uncertainty": "Actual analytical and batch information for the eligible product is unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Chemical form, manufacturing source, dosage form, excipients, and batch/purity records for the eligible product" }, { "item_id": "N04", "question_type": "Dose and total exposure", "question": "Were the original dose and the actual dosing frequency, dietary intake, and concurrent supplements contributing to total exposure distinguished?", "needed": "Dose, dosing frequency, administration records, dietary/concurrent supplement intake, and actual exposure", "role": "Required", "role_reason": "Needed to avoid recasting a nominal dose from another regimen as an effective dose for reducing breakage frequency.", "application_exception": "Preserve the original studies' 2.5 mg/day and 10 mg/day, but do not perform new conversions, identify an optimal dose, or give individual dosing recommendations.", "criterion": "Distinguish each study's originally stated dose from the unverified eligible regimen.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "If dose-specific questions are needed in a direct comparison that collects total exposure and adherence, design them separately in advance.", "current_reports": [ "S23", "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Floersheim's 2.5 mg/day and Chiavetta's 10 mg/day remain in the original text. The former concerns a hardness response, and the latter compares severity with biotin added to the same lacquer; the dose, dosing frequency, and dietary/concurrent supplement intake for an eligible breakage-event regimen are null.", "condition_status": "Partly verified", "status_reason": "The stated doses in the two materials are verified, but they do not establish an effective dose or total exposure for the target breakage events.", "missingness": "The eligible dose, dosing frequency, total dietary/supplement intake, and dose–effect relationship are unverified.", "uncertainty": "The eligible dose, dosing frequency, total dietary/supplement intake, and dose–effect relationship are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Dose, dosing frequency, administration records, dietary/concurrent supplement intake, and actual exposure" }, { "item_id": "N05", "question_type": "Treatment and observation periods", "question": "Are the treatment duration and the prespecified observation period for counting recurrent breakage each verified?", "needed": "Treatment start/end, prespecified event observation window, and follow-up/missingness records at each time point", "role": "Required", "role_reason": "Needed to prevent the number of treatment months from being used as event observation time.", "application_exception": "Preserve study treatment durations, but do not assume that events were captured completely during those periods.", "criterion": "Link treatment duration, event observation period, and exposure time as separate items.", "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; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Set the same observation window for both arms and collect individual observation time and discontinuation/missingness data to distinguish event counts from event rates.", "current_reports": [ "S23", "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Floersheim's mean of 5.5 ± 2.3 months and Chiavetta's 4 months of treatment remain recorded, but the prespecified observation period and individual exposure time for eligible recurrent breakage events were not verified.", "condition_status": "Unverified", "status_reason": "Treatment duration alone does not meet the condition of a defined observation window for recurrent events.", "missingness": "An identical event observation period, complete follow-up, and individual observation times are unverified.", "uncertainty": "An identical event observation period, complete follow-up, and individual observation times are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Treatment start/end, prespecified event observation window, and follow-up/missingness records at each time point" }, { "item_id": "N06", "question_type": "Brittle-nail population", "question": "Do the actual diagnoses and severity in the materials match adults with general brittle nails?", "needed": "Age, diagnosis/severity, inclusion/exclusion, secondary causes, and the composition of mixed populations", "role": "Required", "role_reason": "Needed to avoid pooling other secondary disease, trauma, or drug-related causes with general brittle nails.", "application_exception": "Retain mixed populations as well, but leave direct applicability unverified when population composition or separate results are unavailable.", "criterion": "Distinguish the question's scope of general adults, how the actual population matches it, and exclusions that could not be verified.", "basis": "M03 §3.2.1; detailed population conditions are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Report selection flow and baseline characteristics by site in a population whose secondary causes and severity have been verified.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The question is fixed to adults with general brittle nails and excludes confirmed deficiency correction and specific disease, trauma, or drug-related causes. Actual eligible diagnostic criteria and baseline severity are not_verified.", "condition_status": "Partly verified", "status_reason": "The question's population boundary has been preserved, but actual participant selection criteria for a direct event study are unavailable.", "missingness": "Diagnosis, baseline severity, exclusion of secondary causes, and representativeness are unverified.", "uncertainty": "Diagnosis, baseline severity, exclusion of secondary causes, and representativeness are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Age, diagnosis/severity, inclusion/exclusion, secondary causes, and the composition of mixed populations" }, { "item_id": "N07", "question_type": "Baseline biotin status", "question": "Are baseline biotin testing and the method used to determine deficiency verified?", "needed": "Baseline testing, deficiency definition, diet, concurrent supplements, and whether confirmed deficiency was corrected", "role": "Required", "role_reason": "Needed to avoid treating an unreported status as normal or nondeficient.", "application_exception": "Separate confirmed deficiency correction from this general brittle-nail question. Retain applicability limitations without deleting all data from participants whose status was not measured.", "criterion": "Distinguish actually measured status from unreported status, and do not invent an arbitrary criterion for normality.", "basis": "M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Record the assay method and classification criteria and analyze the deficiency-correction stratum separately, without making arbitrary subgroup efficacy determinations.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original text explicitly states that unreported baseline biotin status is not presumed to mean absence of deficiency. baseline_biotin, deficiency_assay, and dietary_biotin remain null.", "condition_status": "Unverified", "status_reason": "Baseline biotin status and deficiency classification in the direct breakage-event population were not verified.", "missingness": "Baseline status, assay methods, and applicable deficiency criteria are unverified.", "uncertainty": "Baseline status, assay methods, and applicable deficiency criteria are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Baseline testing, deficiency definition, diet, concurrent supplements, and whether confirmed deficiency was corrected" }, { "item_id": "N08", "question_type": "Fingernail and toenail strata", "question": "Are the actual observed sites, numbers observed, and direct recurrent breakage-event results verified separately for fingernails and toenails?", "needed": "Fingernails/toenails, target sites, numbers observed, and site-specific results and denominators", "role": "Required", "role_reason": "Needed to avoid transferring great-toenail severity results to fingernail breakage frequency.", "application_exception": "Retain null values when direct results by site are unavailable, and do not mechanically produce two completed tables.", "criterion": "Check the extent of verification of actual observed sites, numbers of nails, and site-specific recurrent-event results and denominators. Distinguish materials in which only great-toenail severity was verified from the gap in direct event results by site.", "basis": "M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prespecify event definitions and measurements by site, and plan appropriate stratified comparisons and interaction analyses.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The two strata, fingernails and toenails, have direct_result_verified=false and effect=null. Chiavetta is retained as great-toenail severity data and was not transferred to fingernail event frequency.", "condition_status": "Partly verified", "status_reason": "The question's site strata and the location of the great-toenail data are verified, but no direct recurrent-event effect in either stratum was verified.", "missingness": "Fingernail/toenail-specific event results, denominators, and effects, and the actual number of nails observed, are unverified.", "uncertainty": "Fingernail/toenail-specific event results, denominators, and effects, and the actual number of nails observed, are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Fingernails/toenails, target sites, numbers observed, and site-specific results and denominators" }, { "item_id": "N09", "question_type": "Breakage-event definition", "question": "Were the breakage-event definition, collection method, and recurrent-event recording fixed in advance?", "needed": "Event identification, distinction between recurrent/new events, recording intervals, validation, and assessor blinding", "role": "Required", "role_reason": "Needed to avoid converting splitting presence or severity scores into event counts.", "application_exception": "Subjective event reports may also be retained, but their actual definitions and measurement limitations must be disclosed. Do not impose blinding unconditionally.", "criterion": "Clearly distinguish recurrent breakage events per person from severity and responder measures.", "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", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Use identical event definitions and diary/validation procedures, and manage recurrent-event recording, duplicate entries, and missing measurements.", "current_reports": [ "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The primary endpoint of breakage-event counts per person over a prespecified period is stated at the question level. The actual eligible event definition, observation window, and collection method are null; PGA, OGSS, thickness, and hardness do not replace them.", "condition_status": "Unverified", "status_reason": "The exact actual method for collecting recurrent events is absent from the current input.", "missingness": "Event identification, duplicate recording of the same event, differentiation of new breakage, measurement validation, and arm-specific procedures are unverified.", "uncertainty": "Event identification, duplicate recording of the same event, differentiation of new breakage, measurement validation, and arm-specific procedures are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Event identification, distinction between recurrent/new events, recording intervals, validation, and assessor blinding" }, { "item_id": "N10", "question_type": "Person, nail, and event denominators", "question": "Were the numbers of people allocated and analyzed, the number of nails observed, and recurrent-event counts distinguished?", "needed": "Arm-specific counts of people allocated/analyzed/completing follow-up, nails, and events, and observation time", "role": "Required", "role_reason": "Needed to avoid converting the number of evaluable people into a denominator for observed nails, events, or event rates.", "application_exception": "Preserve the denominators in case materials and abstracts, but do not calculate unavailable event counts, exposure time, or CIs.", "criterion": "Use only the denominator types supplied by the current input and preserve eligible-event denominators as null.", "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": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Record clustering and recurrence structures for people and nails, and prespecify an analysis denominator suited to the effect of interest.", "current_reports": [ "S20", "S24", "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "In actual_trial_fields, randomized_n, analysis_n, completed_n, and number_of_nails_observed are null. The n field in evidence is a reference to a separate numeric_evidence table, and that table is absent from this input.", "condition_status": "Unverified", "status_reason": "There are insufficient data to connect the denominators described for each study with the analysis denominators for direct breakage events.", "missingness": "Event/person counts, nail counts, individual follow-up time, and actual arm-specific analysis/completer denominators are unverified.", "uncertainty": "Event/person counts, nail counts, individual follow-up time, and actual arm-specific analysis/completer denominators are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Arm-specific counts of people allocated/analyzed/completing follow-up, nails, and events, and observation time" }, { "item_id": "N11", "question_type": "Actual comparator and direction", "question": "Are within-group before–after comparisons and the direction of the actual comparison for added biotin distinguished?", "needed": "Design, actual added ingredients by arm, comparator, and direction of between-group/within-group estimation", "role": "Required", "role_reason": "Needed to avoid presenting before–after improvement as a between-group causal effect.", "application_exception": "Retain add-on comparisons with common topical care, while specifying the effect of interest and the differing endpoint.", "criterion": "Record within-group before–after comparisons, conditional add-on comparisons, and independent controls separately; do not present a planned comparison as an actual comparison.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prespecify the effect of assignment and the direction of analysis in a comparison that maintains identical background care.", "current_reports": [ "S20", "S21", "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Colombo and Hochman are nonrandomized/uncontrolled before–after and response evaluations. Chiavetta is a randomized comparison of biotin added to the same lacquer, but uses a severity endpoint. A direct between-group comparison of breakage events is unverified.", "condition_status": "Partly verified", "status_reason": "The actual contrasts in prior materials can be distinguished, but there is no direct comparison for the selected event endpoint.", "missingness": "Eligible placebo, no-treatment, and usual-care comparisons and the effect of interest are unverified.", "uncertainty": "Eligible placebo, no-treatment, and usual-care comparisons and the effect of interest are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Design, actual added ingredients by arm, comparator, and direction of between-group/within-group estimation" }, { "item_id": "N12", "question_type": "Colombo surrogate endpoints", "question": "Do Colombo's thickness and surface data provide controlled recurrent breakage-event results for biotin alone?", "needed": "Colombo's actual design, surface/thickness measurements, treatment comparator, and event records", "role": "Required", "role_reason": "Needed to distinguish structural and thickness changes from recurrent breakage events.", "application_exception": "Even if healthy comparators are present, verify whether they constitute the same treatment-assignment control. Do not label an older study as a newly read full text.", "criterion": "Check whether the actual ingredient, treatment comparator, and endpoint meet the direct recurrent-event conditions, and preserve the original thickness and surface results.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M03 §3.2.4; internally designed extension boundary", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "In a comparison that collects both thickness and recurrent events, estimate endpoint-specific results and their relationship separately.", "current_reports": [ "S20" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Colombo 1990 is a nonrandomized before–after electron-microscopy observation. The retained English design description explicitly states that the healthy comparator is not a matched randomized treatment control; the endpoints are thickness and surface structure.", "condition_status": "Not met", "status_reason": "The currently verified endpoint and treatment comparator do not meet the selected between-group recurrent breakage-event conditions.", "missingness": "Target breakage-event counts, a comparator with the same background treatment, and denominators/observation windows are unverified.", "uncertainty": "Target breakage-event counts, a comparator with the same background treatment, and denominators/observation windows are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Colombo's actual design, surface/thickness measurements, treatment comparator, and event records" }, { "item_id": "N13", "question_type": "Hochman response evaluation", "question": "Does Hochman's response evaluation provide controlled recurrent breakage-event results over a prespecified period?", "needed": "Original response criteria, participant selection, recall period, comparator, and recurrent-event records", "role": "Required", "role_reason": "Needed to avoid elevating reports of improved hardness or splitting to prospectively specified event records.", "application_exception": "Retain retrospective uncontrolled data as signals and descriptive material, and do not fill in absent time denominators for events.", "criterion": "Compare response criteria, comparator, and observation period with the selected recurrent-event conditions, and preserve mismatched endpoints in their original role.", "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; M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Use the same prospectively specified event definition and observation period, and plan the comparator and handling of missing data.", "current_reports": [ "S21" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Hochman 1993 is a retrospective uncontrolled response evaluation. Subjective improvements in hardness and splitting are preserved, but a control group and time denominators for events were not verified.", "condition_status": "Not met", "status_reason": "The response evaluation does not provide the selected controlled recurrent-event-count results.", "missingness": "The original number of people analyzed, recurrent breakage counts, observation time, and comparator are unverified in the current input.", "uncertainty": "The original number of people analyzed, recurrent breakage counts, observation time, and comparator are unverified in the current input.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original response criteria, participant selection, recall period, comparator, and recurrent-event records" }, { "item_id": "N14", "question_type": "Floersheim person denominators", "question": "In the report of 71 people treated, 45 evaluated, and 41 reporting improved hardness, are the reasons for exclusion from evaluation and the analysis denominators for recurrent breakage events verified?", "needed": "Original data on treated/evaluated/responder denominators, reasons for exclusion, event counts, and comparator", "role": "Required", "role_reason": "Needed to avoid expressing 41 people as a reduction in recurrent-event counts or generalizing a proportion among evaluated people to an effect among everyone treated.", "application_exception": "Retain the person counts in the abstract, but do not infer reasons for exclusion from evaluation or calculate between-group effects or event rates.", "criterion": "Attribute 71, 45, and 41 to their original-text roles as treated, evaluated, and hardness responders, and assess the extent to which reasons for exclusion from evaluation, numbers of nails observed, recurrent-event denominators, and the comparator are verified by actual data. Do not convert person counts into event counts.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; 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": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Report follow-up and reasons for exclusion from evaluation for all allocated participants, and prespecify the recurrent-event analysis population.", "current_reports": [ "S23" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Floersheim reported that, after treatment of 71 people, the 45 evaluable people included 41 with improved firmness/hardness. The 41 is a count of people who improved, not a count of recurrent breakage events per person.", "condition_status": "Partly verified", "status_reason": "The numbers of people treated, evaluated, and responding are verified, but target recurrent-event denominators and reasons for missing data are unavailable.", "missingness": "Reasons why participants were not evaluated, the number of nails observed, event counts, and the comparator are unverified.", "uncertainty": "Reasons why participants were not evaluated, the number of nails observed, event counts, and the comparator are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original data on treated/evaluated/responder denominators, reasons for exclusion, event counts, and comparator" }, { "item_id": "N15", "question_type": "Floersheim duration and dispersion", "question": "For the report of 2.5 mg/day and a mean of 5.5 ± 2.3 months, are actual exposure records, the definition of ±, and the prespecified breakage observation period verified?", "needed": "Original dose and duration, definition of ±, observation window, and administration records", "role": "Required", "role_reason": "Needed to avoid interpreting the ± accompanying variable treatment duration as an SD/SE/CI or a standardized event observation window.", "application_exception": "If the type of ± is not verified in the abstract, retain it as unverified. Do not indicate that the original German full text was read.", "criterion": "Preserve the original dose and mean treatment duration while checking the extent of verification of the type of ±, actual administration records, and the prespecified breakage observation period. Do not assume that the treatment duration's ± is an SD, SE, CI, or standardized event observation window.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations 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, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Specify treatment duration and the event observation window separately, and report actual exposure records and an explanation of dispersion.", "current_reports": [ "S23" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The currently retained abstract summary reports 2.5 mg/day and a mean of 5.5 ± 2.3 months. The type of ±, a diary, a placebo comparison, and a standardized event window were not verified in the abstract.", "condition_status": "Partly verified", "status_reason": "The stated dose and mean duration were verified, but the type of dispersion and event observation conditions were not verified.", "missingness": "Whether ± denotes SD, SE, or another range, and the actual breakage observation window and adherence, are unverified.", "uncertainty": "Whether ± denotes SD, SE, or another range, and the actual breakage observation window and adherence, are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original dose and duration, definition of ±, observation window, and administration records" }, { "item_id": "N16", "question_type": "Chiavetta add-on design", "question": "Are the allocation, treatment/assessor blinding, and recurrent-event measurement conditions in the comparison of biotin added to the same lacquer actually verified?", "needed": "Lacquer and biotin composition by arm, allocation, treatment/assessor blinding, and target site", "role": "Required", "role_reason": "Needed to distinguish the effect of common topical care, the add-on effect of biotin, and measurement blinding.", "application_exception": "Preserve the fact that assessment was assessor-blinded even with open treatment. Adapt the common background treatment to the sole-active add-on condition while retaining the endpoint mismatch.", "criterion": "Preserve the actual randomized add-on design with open treatment and blinded assessors, and check the extent of verification of allocation concealment, actual adherence, recurrent-event collection, and blinding of event measurement. Do not confirm that event-comparison conditions are met solely from a great-toenail severity assessment.", "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; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Use the same background care and products, and document allocation, measurement and rescue treatment in line with the effect of interest.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Chiavetta was a randomized add-on trial with open treatment and blinded assessors. Both groups used the same hydroxypropyl chitosan lacquer, and severity of the great toenail was assessed.", "condition_status": "Partly verified", "status_reason": "The actual background treatment, design and assessment blinding are verified, but this is not a direct comparison of recurrent breakage events.", "missingness": "Allocation concealment, actual adherence, event collection and blinding of event-endpoint measurement remain unverified.", "uncertainty": "Allocation concealment, actual adherence, event collection and blinding of event-endpoint measurement remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Lacquer and biotin composition by arm, allocation, treatment/assessor blinding, and target site" }, { "item_id": "N17", "question_type": "Chiavetta arm denominators", "question": "For the 24 participants in the add-on group and 26 in the lacquer group, are the actual denominators for allocation, completion, endpoint-specific analysis and recurrent events verified?", "needed": "Arm-specific denominators for allocation, measurement, completion and endpoint analysis, and handling of withdrawals/missing data", "role": "Required", "role_reason": "Required to avoid automatically reusing the number of people in a group as the event count or as the denominator for every endpoint analysis.", "application_exception": "Preserve the 24/26 retained in the source, but do not back-calculate integer responder counts from the proportions.", "criterion": "Compare the reported 24 and 26 participants with the scope of actual verification of arm-specific denominators for completion, endpoint analysis, recurrent events and observation time. Do not reuse participant counts as event counts or as denominators for every endpoint analysis.", "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": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Report the arm-specific flow of people, nails, events and missing data, and separately plan for the effect of assignment and the effect among completers.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The retained Korean text records a comparison of biotin 10 mg/day added for 24 participants versus lacquer alone for 26 participants over 4 months. Denominators for target-event analysis and completion remain unverified in evidence.n and actual_trial_fields.", "condition_status": "Partly verified", "status_reason": "The numbers of people compared and the treatment duration are verified, but these are not recurrent-event counts or the actual denominators for endpoint-specific analysis or completion.", "missingness": "Arm-specific endpoint-analysis/completion denominators, reasons for withdrawal, event counts and observation time remain unverified.", "uncertainty": "Arm-specific endpoint-analysis/completion denominators, reasons for withdrawal, event counts and observation time remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Arm-specific denominators for allocation, measurement, completion and endpoint analysis, and handling of withdrawals/missing data" }, { "item_id": "N18", "question_type": "Positive severity result", "question": "Is Chiavetta's severity reduction of 1.4 versus 0.9 points with P=0.03 a direct recurrent breakage-event result?", "needed": "Original severity scale, change/analysis, score difference, CI and separate event results", "role": "Required", "role_reason": "Required to preserve the positive result without turning it into a reduction in the number of breakages.", "application_exception": "Preserve the nominal between-group P value, but do not calculate a CI, a new difference, an effect size or clinical importance.", "criterion": "Compare the original severity definition behind the positive figures with the conditions for direct recurrent events, and preserve the original values.", "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; separation of statuses is internally designed; M15 §15.3.1–15.3.3; internal application; M03 §3.2.4; internally defined extension boundary", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "If severity and recurrent events are collected together, distinguish each endpoint in advance and report a separate estimate and interval for each.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Chiavetta's reduction in lamellar-splitting severity was 1.4 points in the add-on group versus 0.9 points in the lacquer group, with a between-group P=0.03. The current source text explicitly states that this value is not event frequency.", "condition_status": "Not met", "status_reason": "The positive figures describe a change in severity and do not answer the selected question about recurrent breakage events.", "missingness": "Direct event counts, between-group event differences, CIs and clinical importance remain unverified.", "uncertainty": "Direct event counts, between-group event differences, CIs and clinical importance remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original severity scale, change/analysis, score difference, CI and separate event results" }, { "item_id": "N19", "question_type": "OGSS response criteria", "question": "Do the different OGSS responder proportions meet the conditions for direct recurrent breakage events?", "needed": "Each threshold, responder denominator, analysis, time point, multiple-comparison plan and interval", "role": "Required", "role_reason": "Required to avoid conflating proportions of people who improved and their thresholds with recurrent events or equivalence.", "application_exception": "Improvement of at least 50% and of at least 1 point are different definitions. Do not interpret a nonsignificant finding as equivalence or an effect of 0.", "criterion": "Preserve 80%/53% with P=.05 and 91%/73% with P=.2 under their respective original criteria, and assess whether they match the conditions for direct recurrent events.", "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; separation of statuses is internally designed; M08 §8.2.2, M15 §15.3.1; internal application; M15 §15.3.1–15.3.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prespecify the original response criteria and multiple-comparison plan, and analyze recurrent events as a separate endpoint.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "OGSS improvement of at least 50% was seen in 80% of the add-on group versus 53% of the lacquer group, P=0.05. Improvement of at least 1 point was 91% versus 73%, P=0.2. Each proportion is a responder measure, not a breakage-event rate.", "condition_status": "Not met", "status_reason": "The two response criteria differ from the selected recurrent-event-count conditions. The difference in nominal P values does not warrant a Conflicting information status or imply equivalence.", "missingness": "Actual responder denominators for each criterion, multiple comparisons, CIs and direct event results remain unverified.", "uncertainty": "Actual responder denominators for each criterion, multiple comparisons, CIs and direct event results remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Each threshold, responder denominator, analysis, time point, multiple-comparison plan and interval" }, { "item_id": "N20", "question_type": "Shemer access and results", "question": "Has Shemer's retrospective comparison been documented with the current scope of reading and with direct event results remaining unverified?", "needed": "Product, dose, arm denominators, event collection and analysis in the original full text, and actual scope of access", "role": "Required", "role_reason": "Required to avoid promoting indexed response categories to verified breakage events or full-text results.", "application_exception": "The historical journal 403 and empty PubMed response are not new access failures in the current review, nor do they mean study absence or negative results.", "criterion": "Link the indexed retrospective response categories with the fact that direct event results remain unverified.", "basis": "M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract 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, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed; M08 §8.1–8.2.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "If the full text is obtained, examine the actual comparison, ingredients and event definition, and assess limitations from retrospective selection/recall.", "current_reports": [ "S25" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The Shemer 2025 record documents a retrospective comparison and complete/partial response categories identified in indexed fragments. The historical 403 response from the journal full text and empty response from native PubMed left the dose, arm denominators and standardized event collection unverified. Figures from commercial retellings were not adopted.", "condition_status": "Unverified", "status_reason": "The retained inputs do not contain the full-text coverage needed to verify actual direct event counts, comparisons and methods.", "missingness": "Exact dose, denominators, event diary, standardized observation period and direct between-group effect remain unverified.", "uncertainty": "Exact dose, denominators, event diary, standardized observation period and direct between-group effect remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Product, dose, arm denominators, event collection and analysis in the original full text, and actual scope of access" }, { "item_id": "N21", "question_type": "Patel product boundary", "question": "Does Patel's Sesbania extract isolate the effect of biotin alone on recurrent breakage events?", "needed": "Complete product composition, active ingredients, biotin content and additional ingredients in each arm", "role": "Required", "role_reason": "Required to avoid wrongly attributing contributions from the extract's other ingredients to biotin alone.", "application_exception": "A product described as biotin is different from isolated biotin. Do not import specific product amounts or doses from an adjacent manuscript when those values are absent from the current inputs.", "criterion": "Compare the actual product ingredients and endpoints with the conditions for biotin alone and recurrent events, and use only a contribution that can be isolated as a direct effect.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Directly estimate the ingredient's contribution through a comparison that distinguishes biotin as the sole active ingredient from a control with the same background care.", "current_reports": [ "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Patel's biotin-labeled arm uses a Sesbania extract product. The Korean text for the current 3104 explicitly states that a single-active-ingredient effect cannot be isolated, and does not directly provide exact product content or dosing frequency.", "condition_status": "Not met", "status_reason": "The intervention currently verified does not meet the selected conditions for a direct effect of biotin as the sole active ingredient.", "missingness": "Product amount, purity, the contribution of biotin alone and a regimen eligible for the event question remain unverified and are absent from the current inputs.", "uncertainty": "Product amount, purity, the contribution of biotin alone and a regimen eligible for the event question remain unverified and are absent from the current inputs.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Complete product composition, active ingredients, biotin content and additional ingredients in each arm" }, { "item_id": "N22", "question_type": "Patel endpoint hierarchy conflict", "question": "Does the primary/secondary endpoint hierarchy for Patel's nail PGA agree across Methods, Results and the registry?", "needed": "Original Methods/Results, registry/protocol/SAP, explanation of hierarchy changes and corrections", "role": "Required", "role_reason": "Required to avoid converting severity PGA to event frequency or arbitrarily correcting the hierarchy conflict in the source text.", "application_exception": "Preserve the discrepancy in the hierarchy of the same endpoint between Methods/Results, but do not conclude that selective reporting is established. Do not mark the original PDF containing the conflict as having been read on this occasion.", "criterion": "Compare the PGA 0–5 definition and agreement/disagreement in the Methods/Results primary/secondary hierarchy, and distinguish registry/SAP material that has not been obtained from corrections.", "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; separation of statuses is internally designed; M08 Table 8.2.a, M03 §3.2.4; internal application; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prespecify measurement, endpoint hierarchy and analysis order, and disclose the reasons for changes if the registry and source text disagree.", "current_reports": [ "S05", "S31" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Patel's 0–5-point nail PGA measures peeling, brittleness and surface severity. The current source records conflicting primary/secondary labels for nails in Methods/Results and states that the registry history and analysis plan could not be verified.", "condition_status": "Conflicting information", "status_reason": "This is a discrepancy in the explicitly stated endpoint hierarchy within the same report, not simply a difference between figures from different analyses. Separately, it does not qualify as a direct event result.", "missingness": "Corrections to the conflict, reasons for hierarchy changes, registry history/SAP and recurrent-event results remain unverified.", "uncertainty": "Corrections to the conflict, reasons for hierarchy changes, registry history/SAP and recurrent-event results remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original Methods/Results, registry/protocol/SAP, explanation of hierarchy changes and corrections" }, { "item_id": "N23", "question_type": "Patel analysis population", "question": "Were the statement \"withdrawals excluded\" and the actual denominators for allocation, completion and analysis distinguished?", "needed": "Participant flow by arm, reasons for withdrawal, analysis population and PGA analysis denominators", "role": "Required", "role_reason": "Required to avoid supplementing the statement that withdrawals were excluded with an assumed ITT analysis or arbitrary completer counts.", "application_exception": "Do not import allocation or completion counts from other manuscripts that are absent from the current inputs. Verify allocation, completion and endpoint analysis separately.", "criterion": "Distinguish the actual statement \"withdrawals excluded\" from unverified denominators and the scope of handling.", "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": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Report the flow through allocation, measurement, withdrawal and analysis for each endpoint, and prespecify a plan for sensitivity analyses of missing data.", "current_reports": [ "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Patel's retained English design description records \"randomized double-blind placebo-controlled\" and \"withdrawals excluded.\" The citation refers to historical verification of flowchart/analysis-population locations, but does not provide actual participant counts in this retained summary.", "condition_status": "Partly verified", "status_reason": "The statement that withdrawals were excluded is verified, but actual arm-specific and endpoint-specific denominators and the impact of exclusions remain unverified.", "missingness": "Allocation and completion counts, PGA analysis n, withdrawal reasons, ITT/PP, missing-data handling and event denominators remain unverified.", "uncertainty": "Allocation and completion counts, PGA analysis n, withdrawal reasons, ITT/PP, missing-data handling and event denominators remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Participant flow by arm, reasons for withdrawal, analysis population and PGA analysis denominators" }, { "item_id": "N24", "question_type": "Patel paper and registry family", "question": "For S05 and NCT05972512 in the same F06 family, is material verified that permits comparison of the actual registered endpoint hierarchy, change history and SAP with the paper?", "needed": "Same-trial identifiers, registry history, protocol, SAP and comparison with the paper's results", "role": "Required", "role_reason": "Required to avoid counting the paper and registry record as two independent replication trials.", "application_exception": "The fact that NCT/CTRI identifiers are reported in the paper is distinct from verification of the actual registry history, timing and plan.", "criterion": "Preserve the same-family relationship between S05 and S31, and compare the identifiers reported in the paper with the scope of the registry plan, change history and SAP actually obtained. Do not promote a registry shell to verification of the full plan.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5, §4.6.3; constraints on the current data conversion reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "After linking trial identities, compare the original plan with actual endpoints, time points and analyses, and document the reasons for changes.", "current_reports": [ "S05", "S31" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "F06 in the retained evidence links S05 and S31. The paper reports NCT05972512 and CTRI/2023/11/055359, but only a shell of the actual registry page was obtained historically, leaving the hierarchy, changes and SAP unverified.", "condition_status": "Partly verified", "status_reason": "The relationship identifying the same family is verified, but there is no independent verification of the registry plan, history or results.", "missingness": "Actual registry text, change history, analysis plan and comparison of plans/results remain unverified.", "uncertainty": "Actual registry text, change history, analysis plan and comparison of plans/results remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Same-trial identifiers, registry history, protocol, SAP and comparison with the paper's results" }, { "item_id": "N25", "question_type": "Collagen event data", "question": "Do Hexsel's before-and-after collagen data provide controlled effects of biotin alone on recurrent breakage events?", "needed": "Original text on the actual active substance, control, breakage collection and before-and-after versus between-group analyses", "role": "Required", "role_reason": "Required to avoid importing the effect of a different molecule merely because the endpoint wording is similar.", "application_exception": "Event measurements in studies of other molecules can be retained as pointers for future design, but are not evidence of biotin's effects.", "criterion": "Compare the actual substance, contrast and endpoint with the controlled event conditions for biotin alone, and retain measurement data from another molecule in a separate role.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M08 §8.1–8.2.3; internal application; M08 §8.2.2, M15 §15.3.1; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Even when using methods for collecting breakage frequency as a reference, separately design the control comparison for biotin alone and fix the substance identity.", "current_reports": [ "S26" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Hexsel 2017 provides uncontrolled, open-label before-and-after data on specific bioactive collagen peptides. Even though broken-nail frequency is mentioned, the substance is collagen and this is not a between-group effect of biotin.", "condition_status": "Not met", "status_reason": "The actual active substance and contrast do not match the selected between-group question about biotin alone.", "missingness": "These data do not provide direct recurrent-event results, a control comparison or intervals for biotin.", "uncertainty": "These data do not provide direct recurrent-event results, a control comparison or intervals for biotin.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original text on the actual active substance, control, breakage collection and before-and-after versus between-group analyses" }, { "item_id": "N26", "question_type": "NCT05800496 identity", "question": "Have the PGA wording in the registry shell and the unverified composition and event results been distinguished?", "needed": "Original registry text, composition, actual population/endpoints, status, results and change history", "role": "Required", "role_reason": "Required to avoid overstating the existence of a registry number as acquisition of eligible-product information and trial results.", "application_exception": "Do not turn historical API access failure into a current retrieval failure, negative results, termination or 0 participants.", "criterion": "Separate shell/indexed PGA clues from unverified event results.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed; M04 §4.5, §4.6.3; constraints on the current data conversion reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "If the registry and protocol are obtained, first compare the substance, endpoint, observation window and result identities, then reassess eligibility.", "current_reports": [ "S29" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "NCT05800496 is limited to registry discovery, a page shell and indexed PGA wording. Product composition, protocol, status and results were not verified in the retained review.", "condition_status": "Unverified", "status_reason": "Registry identity clues alone cannot establish the selected between-group results for biotin alone and recurrent breakage.", "missingness": "Product composition, event definition, actual denominators, status and plans/results remain unverified.", "uncertainty": "Product composition, event definition, actual denominators, status and plans/results remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original registry text, composition, actual population/endpoints, status, results and change history" }, { "item_id": "N27", "question_type": "NCT07373574 identity", "question": "Did the review avoid inferring timing, composition or results from the registry number and title?", "needed": "Actual registry text, initiation/changes, composition, endpoints, results and identifiers", "role": "Required", "role_reason": "Required to avoid inventing current trial status or breakage results from search clues.", "application_exception": "Do not infer dates, recruitment or completion status from the order of registry numbers. A nail/hair title is not a direct event definition.", "criterion": "Distinguish the currently verified shell/indexed metadata from what remains unverified by source location.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; constraints on the current data conversion reflect the user-defined scope and internal design; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "After obtaining the formal original registry text, assess agreement in timing, intervention, population and endpoints, and preserve the change history.", "current_reports": [ "S30" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "NCT07373574 is a search/registry identity clue for Effects of Dietary Supplements on Nail and Hair Health. The currently retained source text leaves status, timing, composition and results unverified and did not infer dates from the number.", "condition_status": "Unverified", "status_reason": "There is no registry text available to verify the actual product and direct recurrent-breakage results.", "missingness": "Registry timing, status, product, event definition, denominators and results remain unverified.", "uncertainty": "Registry timing, status, product, event definition, denominators and results remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Actual registry text, initiation/changes, composition, endpoints, results and identifiers" }, { "item_id": "N28", "question_type": "Role of reviews", "question": "Have the discovery and diagnostic context provided by reviews been distinguished from unique direct trials?", "needed": "Review full text, included references, search cutoff date, diagnostic context and links to original trials", "role": "Required", "role_reason": "Required to avoid using a review as evidence of a new randomized replication trial or an up-to-date exhaustive search.", "application_exception": "Preserve older reviews and indexed metadata while distinguishing included trials, citation context and the actual reading scope.", "criterion": "Attribute the roles and access levels of Lipner/Scher, Chessa and Zaraa/Richert to their respective materials.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are internally designed; M03 §3.2.1; detailed population conditions are internally designed; M04 §4.5, §4.6.3; constraints on the current data conversion reflect the user-defined scope and internal design", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Link the original trial families of the included references, examine direct-event eligibility individually and do not substitute an average from a review.", "current_reports": [ "S22", "S27", "S28" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "S22 reused the review extract from the historical 866 record. S27 is a record of review full-text access for diagnostic and treatment discovery context; S28 is limited to the indexed abstract/list for the 2024 online publication/2025 issue. The three reviews are not independent direct trials.", "condition_status": "Partly verified", "status_reason": "The current bibliographic information can be distinguished from historical roles and access levels, but no up-to-date exhaustive review search or reverification of original-trial events was performed.", "missingness": "Direct event results from included trials, search comprehensiveness and complete full-text coverage of some reviews remain unverified.", "uncertainty": "Direct event results from included trials, search comprehensiveness and complete full-text coverage of some reviews remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Review full text, included references, search cutoff date, diagnostic context and links to original trials" }, { "item_id": "N29", "question_type": "Overlap among families and prior verdicts", "question": "Has overlap among same-family reports, repeated citations and previous broad nail verdicts been managed?", "needed": "Report-to-trial families, the same results/time points, boundaries of earlier verdicts and actual overlap identities", "role": "Required", "role_reason": "Required to avoid importing report counts and past grades as independent evidence for the new question.", "application_exception": "F01–F09 are structural family IDs in the current source. Without a separate family table verifying actual overlap, do not establish the final count of unique trials.", "criterion": "Preserve the current evidence families and the S05/S31 link; do not revise or carry forward the different endpoints or original grade of 866.", "basis": "M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed; M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is an internal application; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Link papers, registry records and reviews at the trial level, verify overlap in the original participants and results, then describe independent comparisons.", "current_reports": [ "S05", "S31", "S20", "S21", "S23", "S24", "S25", "S26", "S29", "S30" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The current evidence records F01–F09, and S05/S31 belong to F06. 866 is a broad verdict on thickness, surface, subjective hardness, splitting and overall severity, and is not an exact duplicate of the new breakage-frequency question. Preserve the existing D grade and 28 points only as a historical description in the original source.", "condition_status": "Partly verified", "status_reason": "The retained families and differences from the previous question are verified, but the final number of independent direct trials cannot be established without separate family/audit files.", "missingness": "Complete linkage of original participants, overlapping cohorts and other reports, and the final count of unique direct trials remain unverified.", "uncertainty": "Complete linkage of original participants, overlapping cohorts and other reports, and the final count of unique direct trials remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Report-to-trial families, the same results/time points, boundaries of earlier verdicts and actual overlap identities" }, { "item_id": "N30", "question_type": "Allocation and measurement limitations", "question": "Have allocation and treatment/assessment blinding been reviewed in relation to the actual endpoint concerned?", "needed": "Allocation/concealment, baseline characteristics, event measurement by arm and assessor blinding/verification", "role": "Required", "role_reason": "Required to avoid claiming that recurrent-event measurement/confounding issues are resolved solely from RCT and blinding labels.", "application_exception": "Do not treat inability to blind as automatic failure. Open treatment and blinded assessors can coexist within the same material.", "criterion": "Separate the actual severity-assessment design from the unverified measurement of eligible recurrent events.", "basis": "M08 §8.1–8.2.3; internal application; M08 Table 8.2.a, M03 §3.2.4; internal application; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Document allocation, baseline and measurement procedures, and apply the same event collection and assessment verification in both groups.", "current_reports": [ "S24", "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Chiavetta is retained as an open-treatment/assessor-blinded design, and Patel as a double-blind, placebo-controlled extract design. However, direct event measurement, baseline balance and allocation concealment were not verified.", "condition_status": "Partly verified", "status_reason": "Although the design of the related material is known, the data needed to actually assess bias in the selected direct event result are unavailable.", "missingness": "Eligible allocation, baseline balance, concealment and between-arm differences in event measurement remain unverified.", "uncertainty": "Eligible allocation, baseline balance, concealment and between-arm differences in event measurement remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Allocation/concealment, baseline characteristics, event measurement by arm and assessor blinding/verification" }, { "item_id": "N31", "question_type": "Background care, adherence and rescue care", "question": "Are shared care, concurrent exposure, adherence and rescue treatment actually verified for each arm?", "needed": "Nail care, concurrent products, actual adherence, changes, rescue care and handling in analysis by arm", "role": "Required", "role_reason": "Required to avoid attributing differences in concurrent care or adherence to biotin itself.", "application_exception": "Do not require all changes in both groups to be identical. Distinguish the actual effect of assignment/effect of adherence and the scope of handling.", "criterion": "Document use of the same lacquer separately from unverified concomitant treatment and adherence in the actual eligible event comparison.", "basis": "M03 §3.2.2–3.2.3; reverse-direction marking and test adaptations are internally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prospectively collect data on care, concurrent supplementation, rescue treatment and adherence, and handle them using an analysis aligned with the effect of interest.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Chiavetta's use of the same lacquer is verified, but the actual background_care, rescue_care, adherence and concurrent_supplements for the eligible recurrent-event comparison are all null.", "condition_status": "Unverified", "status_reason": "Identifying the shared lacquer alone does not meet the full conditions for concomitant treatment, adherence and rescue care in the actual event comparison.", "missingness": "Actual treatment continuation, adherence, changes, rescue care and between-arm differences in care remain unverified.", "uncertainty": "Actual treatment continuation, adherence, changes, rescue care and between-arm differences in care remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Nail care, concurrent products, actual adherence, changes, rescue care and handling in analysis by arm" }, { "item_id": "N32", "question_type": "Attrition and estimation", "question": "Are missing data, completer analysis and clustered/recurrent structures linked to the actual effect of interest?", "needed": "Endpoint-specific analysis populations, reasons for missing data/withdrawal, within-participant correlations, adjustment and model/SAP", "role": "Required", "role_reason": "Required to avoid producing precision estimates that ignore correlations involving people, nails and recurrent events, or selective evaluation.", "application_exception": "Preserve the limitations of Floersheim's evaluable participants and Patel's exclusion of withdrawals. Do not fill unreported analyses with ITT, PP or complete follow-up.", "criterion": "Distinguish the currently described scope of withdrawal/evaluation from gaps in eligible direct event analysis.", "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": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Prespecify the flow of allocation, completion and analysis and within-person recurrent-event/nail correlations, and plan sensitivity analyses for missing data.", "current_reports": [ "S23", "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Floersheim reports 71 treated participants with 45 evaluated, and Patel states \"withdrawals excluded,\" but the analysis population, missing-data handling and model for within-person recurrent-event/nail correlations for eligible event results were not verified.", "condition_status": "Unverified", "status_reason": "Some evaluation/withdrawal descriptions are available, but they cannot be linked to the selected direct event estimate and the impact of omissions.", "missingness": "ITT/PP, missing data, adjustment, recurrent/clustered models and effects of discontinuing observation remain unverified.", "uncertainty": "ITT/PP, missing data, adjustment, recurrent/clustered models and effects of discontinuing observation remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Endpoint-specific analysis populations, reasons for missing data/withdrawal, within-participant correlations, adjustment and model/SAP" }, { "item_id": "N33", "question_type": "Effect, interval and importance", "question": "Have the direct between-group breakage-event effect, CI and important difference been reported?", "needed": "Direct between-group event-count estimate, units, denominators, CI, variance and a justified important difference", "role": "Required", "role_reason": "Required to avoid substituting trial count, sample size or nominal P values for the precision or importance of the direct effect.", "application_exception": "If the clinically important difference remains undetermined, retain that status. Do not create a common minimum sample, duration or number of studies, even as proposed numbers.", "criterion": "Distinguish null values for the direct effect, CI, P and MCID from nominal P values for other 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; M15 §15.3.1–15.3.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Plan precision in line with the event distribution, recurrent structure and justified important difference, and report the actual intervals.", "current_reports": [ "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Eligible between_group_effect, CI, P and MCID are all null. Chiavetta's nominal P values for severity/OGSS are retained but do not provide intervals for the event effect.", "condition_status": "Unverified", "status_reason": "No values or criteria are available to interpret the selected direct event estimate or its clinical importance.", "missingness": "Direct between-group event-count differences, CIs, variance and important differences remain unverified.", "uncertainty": "Direct between-group event-count differences, CIs, variance and important differences remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Direct between-group event-count estimate, units, denominators, CI, variance and a justified important difference" }, { "item_id": "N34", "question_type": "Scope of planning and selective reporting", "question": "Can prespecified event endpoints, time points and analyses be compared with actual reporting?", "needed": "Protocol, registry history, SAP, corrections, actual event results and reasons for changes", "role": "Required", "role_reason": "Required to avoid treating registry material that has not been obtained as confirmation of nonregistration or selective reporting.", "application_exception": "Preserve the Patel hierarchy conflict separately. Do not automatically classify unverified plans in other studies as the same conflict.", "criterion": "Distinguish the scope in which plans and reports have been compared from the event questions for which they have not yet been compared.", "basis": "M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and are internally designed; M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Preregister the event definition, window, effect of interest, and multiple comparisons, and report the reasons for changes and all planned outcomes.", "current_reports": [ "S31", "S29", "S30", "S05" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Patel's actual registration history and SAP are unverified, and the historical records also show that the full registry contents for S29/S30 were not acquired. The current input contains no material with which to compare eligible recurrent-event plans and reports.", "condition_status": "Unverified", "status_reason": "There is no material with which to complete a comparison of the formal prespecified event plan with the results. Nonregistration or selective reporting is not established.", "missingness": "Eligible protocols, SAPs, multiple comparisons/changes, and the current status of corrections/retractions are unverified.", "uncertainty": "Eligible protocols, SAPs, multiple comparisons/changes, and the current status of corrections/retractions are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Protocol, registry history, SAP, corrections, actual event results and reasons for changes" }, { "item_id": "N35", "question_type": "Funding, companies, and independence", "question": "Are product provision, funding, and authors' competing interests verified through the actual disclosure wording?", "needed": "Actual wording on disclosed COI, research funding, product provision, author employment/patents, and institutions/study families", "role": "Required", "role_reason": "Needed to prevent historical identification of a COI location or a referenced filename from being treated as proof of independent funding or independent replication.", "application_exception": "Do not automatically exclude a study because of corporate relationships, or judge it independent or free from bias because disclosure wording is absent. Do not infer company names or employment facts absent from the current material.", "criterion": "Distinguish the clues to original COI locations in the current 3104 record from the unverified funding details.", "basis": "Chamgap's own independence and attribution conditions. The official method sections used in this demonstration do not validate all of these detailed items; the distinction between studies and reports in M04 §4.6.1–4.6.2; linking cohorts/outcomes is an internal application", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Disclose product provision, funding sources, analysts' roles, and declarations, and actually verify whether replications share funding/study families.", "current_reports": [ "S20", "S21", "S23", "S24", "S25", "S05", "S26", "S29", "S30" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Each evidence.funding field refers to separate trial_families/evidence_appraisal material. S05 records the product/COI location at pp1–4, and S24 records the funding/conflict location at p4, but this retained summary contains no detailed disclosures or company names. Independence has not been verified.", "condition_status": "Unverified", "status_reason": "Only references and locations of sections read historically are present; the current input contains no actual funding/product provision/employment disclosure wording.", "missingness": "Study-specific funding details, product provision, employment/patents, analytical independence, and independence between study families are unverified.", "uncertainty": "Study-specific funding details, product provision, employment/patents, analytical independence, and independence between study families are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Actual wording on disclosed COI, research funding, product provision, author employment/patents, and institutions/study families" }, { "item_id": "N36", "question_type": "Adverse events by arm", "question": "Are the actual adverse events, discontinuations, and data-collection denominators for this use verified?", "needed": "Adverse-event definitions, collection methods, exposure/events by arm, discontinuations, and loss to follow-up", "role": "Supplementary; required for harm claims", "role_reason": "Needed to prevent safety from being regarded as verified merely because efficacy data exist or harms are unreported.", "application_exception": "Separate recurrent breakage events used to assess efficacy from adverse events. Do not remove other prior efficacy outcomes because harms were unreported.", "criterion": "Separate the verified safety context from the unverified harms by arm for this use.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; M19 §19.1.2–19.2.4, M04 §4.6.3; internal application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Plan systematic adverse-event collection, discontinuation assessment, and follow-up for the same exposure/population, and report denominators and duration by arm.", "current_reports": [ "S06", "S07" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original safety status is Caution. The current source explicitly states that adverse events and discontinuations by arm, and long-term safety/safety in vulnerable groups for use in brittle nails, are unverified.", "condition_status": "Unverified", "status_reason": "There is no direct information on harm collection, denominators, or discontinuations for this use.", "missingness": "Exposure by arm, people with adverse events/event counts, follow-up/discontinuations, and systematic collection are unverified.", "uncertainty": "Exposure by arm, people with adverse events/event counts, follow-up/discontinuations, and systematic collection are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Adverse-event definitions, collection methods, exposure/events by arm, discontinuations, and loss to follow-up" }, { "item_id": "N37", "question_type": "Assay-interference signals", "question": "Are the actual populations, exposures, timing, and assay-specific scope of applicability of interference with thyroid, NT-proBNP, and troponin tests verified?", "needed": "Original assay methods, doses/timing, healthy-participant denominators, collection, official restatements, and limitations", "role": "Supplementary; required to explain assay-related harms", "role_reason": "Needed to prevent assay-dependent interference from being generalized to an identical risk rate or stopping interval for all tests and people.", "application_exception": "Official restatements do not constitute independent case counts. Short-term exposure in healthy people does not answer the question of long-term safety in brittle nails.", "criterion": "Preserve the single/repeated doses, timing, populations, and specific assay signals in the historical material, and compare the scope of verified original material with what is needed for applicability by assay, reagent, and population and for general risk estimation. Do not treat inherited summaries as current reverification of external full texts or as universal risk rates.", "basis": "M19 §19.1.2–19.2.4; internal application; M19 §19.1.2–19.2.4; detailed distinctions are internally designed; design-specific harm questions in M19 §19.2; temporal-relationship details are internally designed; M19 §19.2.2–19.2.4, M03 §3.2.3; internal application; Chamgap's own interpretation boundaries. M19 principles are referenced; no official causality tool was applied", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Verify the scope of interference through assay-specific validation that records applicability conditions such as the assay platform, exposure/blood-sampling times, and renal function.", "current_reports": [ "S06", "S07" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The inherited NIH wording describes interference with some thyroid assays after a single 10 mg dose (within 24 hours), and with some TSH/NT-proBNP assays in 6 healthy people exposed to 10 mg/day for 1 week. The FDA warns of falsely low results in some troponin assays.", "condition_status": "Partly verified", "status_reason": "The assay-specific exposure and denominator signals in the historical manuscript have been preserved, but this is neither current reverification of external original texts nor general risk estimation.", "missingness": "Platform-specific risk rates, an identical stopping interval for all assays, and the scope of assay applicability to this use are unverified.", "uncertainty": "Platform-specific risk rates, an identical stopping interval for all assays, and the scope of assay applicability to this use are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original assay methods, doses/timing, healthy-participant denominators, collection, official restatements, and limitations" }, { "item_id": "N38", "question_type": "Vulnerable groups, intake, and UL", "question": "Are there actual exposure, event, and follow-up data to verify long-term safety and safety during pregnancy/lactation, in children, and in liver or kidney disease for this use?", "needed": "Actual exposure by population, long-term/rare harms, interactions, and original nutritional standards", "role": "Supplementary; required for extended safety claims", "role_reason": "Needed to prevent adequate intake and the absence of an established upper limit from being treated as a therapeutic dose or unlimited safety.", "application_exception": "Not every rare-harm study is required for the current narrow event-efficacy question, but broader safety remains separately unverified.", "criterion": "Assess whether actual exposure, event denominators, and long-term follow-up by population answer the questions underlying extended safety claims. Do not use adequate intake or the absence of an established UL as evidence for a therapeutic dose, an optimal dose, or unlimited safety.", "basis": "M19 §19.1.2–19.2.4; internal application; Chamgap's own interpretation boundaries. M19 principles are referenced; no official causality tool was applied; M03 §3.2.1; detailed population conditions are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "Investigate long-term harms and harms in vulnerable groups through actual use and systematic follow-up by population, and separate nutritional standards from treatment questions.", "current_reports": [ "S06", "S07" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original text explicitly states that adequate intake is not a therapeutic dose for brittle nails and that the absence of an established UL does not mean unlimited safety. Long-term safety and safety during pregnancy and lactation, in children, and in liver or kidney disease for this use are unverified.", "condition_status": "Unverified", "status_reason": "There is no direct denominator/follow-up information to verify safety in broader populations or over the long term.", "missingness": "Long-term and rare harms, exposure/events in each vulnerable group, interactions, and continued follow-up are unverified.", "uncertainty": "Long-term and rare harms, exposure/events in each vulnerable group, interactions, and continued follow-up are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Actual exposure by population, long-term/rare harms, interactions, and original nutritional standards" }, { "item_id": "N39", "question_type": "Extensions to dose, persistence, and anatomical site", "question": "Is there direct material supporting extensions to optimal dose, persistence after discontinuation, or effects by anatomical site?", "needed": "Direct dose comparisons, follow-up after discontinuation/over the long term, anatomical-site strata, and prespecified interactions", "role": "Supplementary; required for the relevant extension", "role_reason": "Needed to prevent short-term or variable-duration treatment data on other endpoints from being treated as evidence for an optimal regimen or persistent effects.", "application_exception": "Do not require every extension study for the narrow assessment target. Retain each as a separate research question and gap.", "criterion": "Distinguish the unverified main effect from the separate lack of direct verification for extensions to dose, persistence, or anatomical site.", "basis": "M03 §3.2.1–3.2.4; dose, persistence, and effect-modification details are internally designed; M03 §3.2.1; detailed population conditions are internally designed; M03 §3.2.2–3.2.3; reverse-direction labeling and assay adaptations are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "When extension questions are actually needed, design separate comparisons with prespecified hypotheses on dose, follow-up after discontinuation, and anatomical site.", "current_reports": [ "S23", "S24" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "Hardness responses to 2.5 mg/day over variable durations and great-toenail severity with 10 mg/day over 4 months do not constitute a direct dose comparison. Site-specific event effects, persistence after discontinuation, and the optimal dose have not been verified.", "condition_status": "Unverified", "status_reason": "The current material contains no direct dose, follow-up, or interaction estimates that answer these extensions of the breakage-event question.", "missingness": "Optimal dose, effects during maintenance/after discontinuation, and effect modification by anatomical site are unverified.", "uncertainty": "Optimal dose, effects during maintenance/after discontinuation, and effect modification by anatomical site are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Direct dose comparisons, follow-up after discontinuation/over the long term, anatomical-site strata, and prespecified interactions" }, { "item_id": "N40", "question_type": "Current and historical reading", "question": "Has the actual reading of local retained summaries in this review been separated from historical external access, failures, and inherited material?", "needed": "Each material's identity, actual material type, URL, existence/public availability/access/acquisition/reading, and original location/date", "role": "Required", "role_reason": "Needed to prevent bibliographic information, URLs, or historical full-text records from being treated as acquisition or reading of original material in this review.", "application_exception": "No attempt at external access is different from failure. If the actual access date is absent from the source, leave it null and separate it from the original review date of 2026-09-15.", "criterion": "Mark the preserved retained summaries as read in this review, and separately mark external materials as access not attempted, not acquired, and Not read.", "basis": "Material collection/selection principles in M04 §4.5–4.6; the 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 are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "When original material is actually acquired, record the timing, safe URL, material type, and content location separately, and preserve the historical original text.", "current_reports": [ "S05", "S06", "S07", "S20", "S21", "S22", "S23", "S24", "S25", "S26", "S27", "S28", "S29", "S30", "S31" ], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The complete Korean, English, structured, and bibliographic summaries in the current source were actually read. Historical author HTML access/failed PDF download for S24, historical limitations for S25/S29/S30, and inherited-material labels for S06/S07 are historical records. Access to all external materials was unattempted and none were read in this review.", "condition_status": "Met", "status_reason": "Record current local reading separately from the original source access_level/location and review date, without claiming successful external access.", "missingness": "Current external existence, public availability, acquisition, and full-text reading, as well as individual access dates absent from the source, are unverified.", "uncertainty": "Current external existence, public availability, acquisition, and full-text reading, as well as individual access dates absent from the source, are unverified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Each material's identity, actual material type, URL, existence/public availability/access/acquisition/reading, and original location/date" }, { "item_id": "N41", "question_type": "Original verdict and scope of absence", "question": "Have the original ?/null, B/P, document quality, and the scope of unverified direct evidence been preserved?", "needed": "Original verdict/axes, scope of absence, related human material, document quality, and self-review metadata", "role": "Required", "role_reason": "Needed to prevent bounded stage0 from being treated as an effect of 0, an absence of human studies, or a new score.", "application_exception": "human_study_exists=false/no_human_study=true refers to eligible direct results for the fixed question and is compatible with related_human_studies_exist=true.", "criterion": "Preserve grade ?, score null, B/P, subsequent axes null, bounded scope, and document quality A unchanged.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and are internally designed; M03 §3.2.4; internally defined extension boundaries", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "When new direct material is actually received, review an update to the original verdict and a change to the table's condition version as separate events, without automatic rescoring.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original grade is ?, score is null, and safety is Caution. The subsequent axes after the B/P question classification are null, and related_human_studies_exist=true. The scope of no_human_study is this sole-active-ingredient, controlled recurrent-event question. document_quality A and single-assistant self-review are neither efficacy findings nor external clinical certification.", "condition_status": "Met", "status_reason": "The original verdict, classification, and limitation metadata were preserved as a conversion record; no new effect, grade, or clinical certification was created.", "missingness": "Direct effects, the count of unique direct trials, worldwide absence, and a new official reassessment were not verified.", "uncertainty": "Direct effects, the count of unique direct trials, worldwide absence, and a new official reassessment were not verified.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Original verdict/axes, scope of absence, related human material, document quality, and self-review metadata" }, { "item_id": "N42", "question_type": "Boundaries for updates and follow-up material", "question": "To what extent have follow-up material, corrections/retractions, and public release status actually been verified in relation to the original revision policy and the current authoring history?", "needed": "Complete pre-change content, material/condition/verdict events, version, original location, and current verification date", "role": "Required", "role_reason": "Needed to prevent creation of new retained summaries or passage of technical checks from being confused with a current clinical verdict or completed public release.", "application_exception": "The historical server_deployed value in the current manuscript does not represent deployment of the new gap table. If conditions change, preserve the entire original text, then freeze the new version before applying it.", "criterion": "Link the original revision policy with the current preservation, freezing, and application history, and assess subsequent external evidence, corrections/retractions, and publication status within the scope of material actually verified. The existence of a policy or future triggers does not substitute for verification of follow-up material or completed public release.", "basis": "Material collection/selection principles in M04 §4.5–4.6; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; status separation is internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user's scope and are internally designed", "condition_origin": "An internally developed condition written individually with knowledge of the currently retained materials. This is not clinical preregistration, blinding, or official methodological certification.", "proposed_research": "When follow-up material is received, preserve existing results and historical access records, and review only the relevant rows; handle condition changes separately through freeze→apply.", "current_reports": [], "existence": "Statements and values are present in the currently linked retained summary. This does not verify the current existence of the external material or establish efficacy.", "acquired_read": "Summary read: the current local retained-summary location was read. For the corresponding external material, access was not attempted, and it was neither acquired nor read in this review.", "observation": "The original text records new eligible studies, full texts, registrations, corrections, retractions, and numerical/classification errors as revision triggers. In this work, an individual table of the preserved retained summaries was created; no external material was actually received, original verdict revised, or public deployment performed.", "condition_status": "Partly verified", "status_reason": "The original revision policy has been linked to the current authoring scope, but verification of future material, corrections, or public release is not an action completed in this work.", "missingness": "The latest external corrections/retractions, new evidence, and subsequent publication status are unverified; content QA by another author and format/UI work are the next stage.", "uncertainty": "The latest external corrections/retractions, new evidence, and subsequent publication status are unverified; content QA by another author and format/UI work are the next stage.", "review_date": "2026-10-05", "reading_status": "Original source: Not read · Retained summary read", "additional_material": "Complete pre-change content, material/condition/verdict events, version, original location, and current verification date" } ], "reports": [ { "report_id": "S05", "title": "The Role of Sesbania grandiflora-Derived Biotin and Bambusa arundinacea-Derived Silica Extracts in Promoting Hair, Skin, and Nail Health (Patel et al., 2025)", "url": "https://ophthalmology.cureus.com/articles/385055-the-role-of-sesbania-grandiflora-derived-biotin-and-bambusa-arundinacea-derived-silica-extracts-in-promoting-hair-skin-and-nail-health-a-randomized-double-blind-placebo-controlled-clinical-study.pdf?email=", "report_type": "Placebo-controlled botanical-extract report on nail PGA", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F06", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The arm described as a Sesbania extract in Patel 2025 is not an isolated-biotin sole-active-ingredient product. Nail PGA 0–5 measures peeling, brittleness, and surface severity, not recurrent breakage-event counts. The preserved wording records a Methods/Results endpoint-hierarchy conflict and withdrawals excluded, but this retained summary contains neither actual denominators nor a specific product amount. NCT05972512/CTRI identifies the registration as reported in the paper; the registration history/SAP are unverified.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: full_text_pdf_endpoint_extension. Historical recorded location: Reused pp1–4/19 product and COI; newly checked p5 nail PGA methods and p11 nail Results/Figure5; Methods/Results hierarchy conflict.. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S05-M1", "url": "https://ophthalmology.cureus.com/articles/385055-the-role-of-sesbania-grandiflora-derived-biotin-and-bambusa-arundinacea-derived-silica-extracts-in-promoting-hair-skin-and-nail-health-a-randomized-double-blind-placebo-controlled-clinical-study.pdf?email=", "bibliographic_url": "https://ophthalmology.cureus.com/articles/385055-the-role-of-sesbania-grandiflora-derived-biotin-and-bambusa-arundinacea-derived-silica-extracts-in-promoting-hair-skin-and-nail-health-a-randomized-double-blind-placebo-controlled-clinical-study.pdf?email=" } ], "links": [ { "label": "Source", "url": "https://ophthalmology.cureus.com/articles/385055-the-role-of-sesbania-grandiflora-derived-biotin-and-bambusa-arundinacea-derived-silica-extracts-in-promoting-hair-skin-and-nail-health-a-randomized-double-blind-placebo-controlled-clinical-study.pdf?email=" } ] }, { "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": "Inherited official context on nutrition and assay interference", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "OFFICIAL-NIH-BIOTIN", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The NIH access record in the current 3104 material is inherited_official_extract, carrying forward the original prior verification; even then, it was not a new fetch or reverification of current status. It preserves interference signals for some thyroid assays after a single 10 mg dose (within 24 hours), and for some TSH/NT-proBNP assays in 6 healthy people exposed to 10 mg/day for 1 week. Adequate intake is not a therapeutic dose, and the absence of an established UL does not mean unlimited safety.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the official web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: inherited_official_extract. Historical recorded location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S06-M1", "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": "Inherited warning for specific troponin assays", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "OFFICIAL-FDA-BIOTIN", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The FDA warning about falsely low results in some troponin assays is official safety context inherited by the manuscript. It does not mean an identical risk rate or stopping interval across all assays and exposures. Do not use it as evidence of efficacy for breakage frequency or as individual safety/dosing instructions.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the official web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: inherited_official_extract. Historical recorded location: Opening safety statement and paragraphs on residual assay interference. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S07-M1", "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": "S20", "title": "Colombo et al. 1990: Treatment of brittle fingernails and onychoschizia with biotin: scanning electron microscopy", "url": "https://pubmed.ncbi.nlm.nih.gov/2273113/", "report_type": "Nonrandomized before-and-after electron-microscopy data on thickness and surface", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F01", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "Colombo 1990 observes thickness and surface, not direct recurrent breakage events. The healthy comparators are not a matched randomized treatment control, and event denominators are unverified. The original summary/source identifier remains an extract supplied from the earlier 866 record; the old original text was not opened in this review.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the bibliographic/abstract web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: provided_extract. Historical recorded location: historical reference record 866.json: evidence Colombo entry and corresponding citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S20-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/2273113/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/2273113/" }, { "material_type": "Full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: provided_extract. Historical recorded location: historical reference record 866.json: evidence Colombo entry and corresponding citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S20-M2", "url": null, "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/2273113/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/2273113/" } ] }, { "report_id": "S21", "title": "Hochman et al. 1993: Brittle nails: response to daily biotin supplementation", "url": "https://pubmed.ncbi.nlm.nih.gov/8477615/", "report_type": "Retrospective uncontrolled hardness/splitting responses", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F02", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "Hochman 1993 provides retrospective uncontrolled data on subjective hardness/splitting responses. A prespecified recurrent-event observation window, time denominator, and between-group effect have not been verified. Only the supplied earlier extract was read; a null DOI field is not described as absence of a DOI itself.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the bibliographic/abstract web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: provided_extract. Historical recorded location: historical reference record 866.json: evidence Hochman entry and citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S21-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/8477615/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/8477615/" }, { "material_type": "Full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: provided_extract. Historical recorded location: historical reference record 866.json: evidence Hochman entry and citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S21-M2", "url": null, "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/8477615/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/8477615/" } ] }, { "report_id": "S22", "title": "Lipner and Scher: Biotin for the treatment of nail disease: what is the evidence?", "url": "https://pubmed.ncbi.nlm.nih.gov/29057689/", "report_type": "Review reused from the earlier verdict as discovery context", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "REVIEW-LIPNER-SCHER", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The Lipner/Scher review is a provided_review_extract from the earlier 866 record. It is preserved as discovery context and is not counted as an independent randomized replication, a current exhaustive search, or evidence of study absence. Neither the original review nor the old 866 file was opened in this review.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the bibliographic/abstract web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: provided_review_extract. Historical recorded location: historical reference record 866.json: review evidence/citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S22-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/29057689/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/29057689/" }, { "material_type": "Full text of the review paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: provided_review_extract. Historical recorded location: historical reference record 866.json: review evidence/citation. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S22-M2", "url": null, "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/29057689/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/29057689/" } ] }, { "report_id": "S23", "title": "Floersheim 1989: Treatment of brittle fingernails with biotin", "url": "https://pubmed.ncbi.nlm.nih.gov/2648686/", "report_type": "Treatment observations of hardness responses within the scope of the English abstract", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F03", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The Floersheim 1989 figures are preserved: 71 people treated, 45 evaluated, and 41 with improved hardness; 2.5 mg/day for a mean of 5.5 ± 2.3 months. The type of ±, placebo comparison, event diary, and standardized observation window are unverified in the abstract. The 41 people are the number of people who responded, not recurrent-event counts per person. The English PubMed abstract was read historically; this does not represent current reading of the German original full text.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the bibliographic/abstract web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: abstract. Historical recorded location: PubMed Abstract, paragraphs on 71 treated / 45 evaluated / 41 firmer-hardness responses and treatment duration. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S23-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/2648686/", "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/2648686/" }, { "material_type": "Full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: abstract. Historical recorded location: PubMed Abstract, paragraphs on 71 treated / 45 evaluated / 41 firmer-hardness responses and treatment duration. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S23-M2", "url": null, "bibliographic_url": "https://pubmed.ncbi.nlm.nih.gov/2648686/" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/2648686/" } ] }, { "report_id": "S24", "title": "Chiavetta et al. 2019: Hydroxypropyl chitosan-based lacquer alone or with oral biotin", "url": "https://www.researchgate.net/publication/334685659_Treatment_of_brittle_nail_with_a_hydroxypropyl_chitosan-based_lacquer_alone_or_in_combination_with_oral_biotin_A_randomized_assessor-blinded_trial", "report_type": "Conditional biotin add-on comparison for great-toenail severity", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F04", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "Chiavetta 2019 is a randomized add-on study with open treatment and blinded assessment. It compared biotin 10 mg/day added to the same lacquer in 24 people versus lacquer in 26 people over 4 months. Splitting-severity reductions of 1.4 versus 0.9 points, P=0.03; OGSS improvement of 50% or more in 80% versus 53%, P=0.05; and improvement of 1 point or more in 91% versus 73%, P=0.2, are different endpoints/response criteria. They were not converted into recurrent breakage events. Historical author HTML access and PDF download failure are distinguished from reading in this review.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the author-uploaded web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: author_posted_full_text. Historical recorded location: Author-posted accepted manuscript: pp1–2 Methods target great toenail and OGSS; pp2–3 Results; p4 funding/conflict statement. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S24-M1", "url": "https://www.researchgate.net/publication/334685659_Treatment_of_brittle_nail_with_a_hydroxypropyl_chitosan-based_lacquer_alone_or_in_combination_with_oral_biotin_A_randomized_assessor-blinded_trial", "bibliographic_url": "https://www.researchgate.net/publication/334685659_Treatment_of_brittle_nail_with_a_hydroxypropyl_chitosan-based_lacquer_alone_or_in_combination_with_oral_biotin_A_randomized_assessor-blinded_trial" }, { "material_type": "Publisher full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: author_posted_full_text. Historical recorded location: Author-posted accepted manuscript: pp1–2 Methods target great toenail and OGSS; pp2–3 Results; p4 funding/conflict statement. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S24-M2", "url": null, "bibliographic_url": "https://www.researchgate.net/publication/334685659_Treatment_of_brittle_nail_with_a_hydroxypropyl_chitosan-based_lacquer_alone_or_in_combination_with_oral_biotin_A_randomized_assessor-blinded_trial" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/334685659_Treatment_of_brittle_nail_with_a_hydroxypropyl_chitosan-based_lacquer_alone_or_in_combination_with_oral_biotin_A_randomized_assessor-blinded_trial" } ] }, { "report_id": "S25", "title": "Shemer et al. 2025: Biotin or Pyridoxine Versus Combined Regimen in Treatment of Onychoschizia", "url": "https://jddonline.com/articles/biotin-or-pyridoxine-versus-combined-regimen-in-treatment-of-onychoschizia-S1545961625P7687X", "report_type": "Indexed response-category fragments from a recent retrospective comparison", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F05", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The Shemer 2025 record states that retrospective comparison and complete/partial response were identified in the index. A full journal response of 403 and an empty native PubMed response prevented verification of dose, arm denominators, and standardized recurrent-event collection. These access limitations are neither negative results nor study absence; figures from commercial restatements were not adopted.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the journal web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: indexed_primary_abstract_fragments. Historical recorded location: Indexed journal/institutional abstract fragments: retrospective comparison, response categories; full journal page returned 403. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S25-M1", "url": "https://jddonline.com/articles/biotin-or-pyridoxine-versus-combined-regimen-in-treatment-of-onychoschizia-S1545961625P7687X", "bibliographic_url": "https://jddonline.com/articles/biotin-or-pyridoxine-versus-combined-regimen-in-treatment-of-onychoschizia-S1545961625P7687X" }, { "material_type": "Full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: indexed_primary_abstract_fragments. Historical recorded location: Indexed journal/institutional abstract fragments: retrospective comparison, response categories; full journal page returned 403. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S25-M2", "url": null, "bibliographic_url": "https://jddonline.com/articles/biotin-or-pyridoxine-versus-combined-regimen-in-treatment-of-onychoschizia-S1545961625P7687X" } ], "links": [ { "label": "Source", "url": "https://jddonline.com/articles/biotin-or-pyridoxine-versus-combined-regimen-in-treatment-of-onychoschizia-S1545961625P7687X" } ] }, { "report_id": "S26", "title": "Hexsel et al. 2017: Oral supplementation with specific bioactive collagen peptides improves nail growth and reduces symptoms of brittle nails", "url": "https://www.researchgate.net/publication/318989437_Oral_supplementation_with_specific_bioactive_collagen_peptides_improves_nail_growth_and_reduces_symptoms_of_brittle_nails", "report_type": "Uncontrolled breakage-frequency data for another substance, collagen", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F07", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "Hexsel 2017 is an uncontrolled open-label before-and-after study of collagen peptides. Even though broken-nail frequency is reported, it is not a biotin between-group effect. Only the manuscript record of author HTML access/a direct PubMed challenge is preserved; the external original text was not read in this review.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the author-uploaded web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: author_posted_full_text. Historical recorded location: Abstract and Methods: collagen peptides, uncontrolled design, broken-nail frequency. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S26-M1", "url": "https://www.researchgate.net/publication/318989437_Oral_supplementation_with_specific_bioactive_collagen_peptides_improves_nail_growth_and_reduces_symptoms_of_brittle_nails", "bibliographic_url": "https://www.researchgate.net/publication/318989437_Oral_supplementation_with_specific_bioactive_collagen_peptides_improves_nail_growth_and_reduces_symptoms_of_brittle_nails" }, { "material_type": "Publisher full text of the paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: author_posted_full_text. Historical recorded location: Abstract and Methods: collagen peptides, uncontrolled design, broken-nail frequency. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S26-M2", "url": null, "bibliographic_url": "https://www.researchgate.net/publication/318989437_Oral_supplementation_with_specific_bioactive_collagen_peptides_improves_nail_growth_and_reduces_symptoms_of_brittle_nails" } ], "links": [ { "label": "Source", "url": "https://www.researchgate.net/publication/318989437_Oral_supplementation_with_specific_bioactive_collagen_peptides_improves_nail_growth_and_reduces_symptoms_of_brittle_nails" } ] }, { "report_id": "S27", "title": "Chessa et al.: Pathogenesis, Clinical Signs and Treatment Recommendations in Brittle Nails: A Review", "url": "https://link.springer.com/article/10.1007/s13555-019-00338-x", "report_type": "Review providing context on diagnosis, causes, and treatment", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "REVIEW-CHESSA", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "The Chessa review provides discovery context for causes, diagnosis, treatment, and biotin references. The historical PMC challenge and publisher HTML access are distinguished. The review is not counted as a unique event-comparison trial or an eligible effect.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the review paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: full_text_review. Historical recorded location: Causes/diagnosis and treatment sections; biotin references. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S27-M1", "url": "https://link.springer.com/article/10.1007/s13555-019-00338-x", "bibliographic_url": "https://link.springer.com/article/10.1007/s13555-019-00338-x" } ], "links": [ { "label": "Source", "url": "https://link.springer.com/article/10.1007/s13555-019-00338-x" } ] }, { "report_id": "S28", "title": "Zaraa and Richert: Nail Supplements: When, How, and Why?", "url": "https://karger.com/sad/article/11/2/176/913681/Nail-Supplements-When-How-and-Why", "report_type": "Review at the level of online/issue metadata and abstract", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "REVIEW-ZARAA-RICHERT", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "Zaraa/Richert was preserved at the level of the indexed abstract and reference list for the 2024 online publication/2025 issue. This is neither full-text primary-outcome verification nor an independent clinical trial. The PMC challenge reflects the historical scope of access; no query was made in this review.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the publisher web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: indexed_review_metadata_abstract. Historical recorded location: Publisher indexed abstract and reference list; PMC challenge. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S28-M1", "url": "https://karger.com/sad/article/11/2/176/913681/Nail-Supplements-When-How-and-Why", "bibliographic_url": "https://karger.com/sad/article/11/2/176/913681/Nail-Supplements-When-How-and-Why" }, { "material_type": "Full text of the review paper", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: indexed_review_metadata_abstract. Historical recorded location: Publisher indexed abstract and reference list; PMC challenge. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S28-M2", "url": null, "bibliographic_url": "https://karger.com/sad/article/11/2/176/913681/Nail-Supplements-When-How-and-Why" } ], "links": [ { "label": "Source", "url": "https://karger.com/sad/article/11/2/176/913681/Nail-Supplements-When-How-and-Why" } ] }, { "report_id": "S29", "title": "ClinicalTrials.gov NCT05800496: nail supplement trial record", "url": "https://clinicaltrials.gov/study/NCT05800496", "report_type": "NCT05800496 registry shell and indexed PGA clues", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F08", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "NCT05800496 is limited to the shell/indexed nail PGA wording and the historical API failure. Full composition, protocol, status, results, and event definition are unverified. It is not counted as a negative trial, a terminated trial, or a trial with 0 participants.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the registry web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: registration_shell_and_indexed_snippet. Historical recorded location: Page shell; indexed nail PGA wording; API failed. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S29-M1", "url": "https://clinicaltrials.gov/study/NCT05800496", "bibliographic_url": "https://clinicaltrials.gov/study/NCT05800496" }, { "material_type": "Full text of the study protocol/analysis plan", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: registration_shell_and_indexed_snippet. Historical recorded location: Page shell; indexed nail PGA wording; API failed. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S29-M2", "url": null, "bibliographic_url": "https://clinicaltrials.gov/study/NCT05800496" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT05800496" } ] }, { "report_id": "S30", "title": "ClinicalTrials.gov NCT07373574: Effects of Dietary Supplements on Nail and Hair Health", "url": "https://clinicaltrials.gov/study/NCT07373574", "report_type": "NCT07373574 registry shell and search-metadata clues", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F09", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "NCT07373574 records search discovery of a nail/hair title and a page shell/API failure. Current status, timing, composition, and results have not been verified. Do not infer dates or recruitment status from the number.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the registry web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: registration_shell_and_indexed_metadata. Historical recorded location: Page shell; API failed. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S30-M1", "url": "https://clinicaltrials.gov/study/NCT07373574", "bibliographic_url": "https://clinicaltrials.gov/study/NCT07373574" }, { "material_type": "Full text of the study protocol/analysis plan", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: registration_shell_and_indexed_metadata. Historical recorded location: Page shell; API failed. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S30-M2", "url": null, "bibliographic_url": "https://clinicaltrials.gov/study/NCT07373574" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT07373574" } ] }, { "report_id": "S31", "title": "ClinicalTrials.gov NCT05972512: identifier reported by Patel study", "url": "https://clinicaltrials.gov/study/NCT05972512", "report_type": "Same family as S05: NCT05972512 registration", "existence": "This is a reference to retained bibliographic information and historical records; the current external response has not been verified.", "acquired_read": "The relevant Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original material was not read in this review.", "study_family": "F06", "independent_replication": "Only the family_id and citation relationships in the current source are linked. The 15 citations and 9 structured families are not a count of independent eligible direct trials.", "observed_result": "NCT05972512 is the same family identifier reported by the Patel paper S05. The actual registry endpoint hierarchy, changes, and SAP were not historically retrievable; only a shell remains. The paper and registration are not counted as two independent trials.", "result_level": "This content is recorded in the retained manuscript. It is not the result of a new comparison against external original material in this review.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of the registry web document", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. This is the entry URL recorded for the retained material; it does not verify current access or full-text acquisition. Historical access level recorded for the report as a whole: registration_shell. Historical recorded location: Article S05 registration citation; actual registry page shell only. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S31-M1", "url": "https://clinicaltrials.gov/study/NCT05972512", "bibliographic_url": "https://clinicaltrials.gov/study/NCT05972512" }, { "material_type": "Full text of the study protocol/analysis plan", "public_status": "Unverified (no external query in this review)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "Material type, bibliographic links, and historical reading are separate from the fact that this external material was not read in this review. No access to this external material was attempted and its full text was not read in this review. What was read in this review consists of the retained report summaries. The current record contains no direct URL for this material type. Bibliographic information/author uploads are not treated as publisher full text or a protocol download. Historical access level recorded for the report as a whole: registration_shell. Historical recorded location: Article S05 registration citation; actual registry page shell only. This historical report-level status is not inherited as the current reading status of each material. The actual historical access date for each material is unverified. The retained manuscript review date of 2026-09-15 is not the access date for the original material.", "material_id": "S31-M2", "url": null, "bibliographic_url": "https://clinicaltrials.gov/study/NCT05972512" } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT05972512" } ] } ], "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 document the question, eligibility conditions, and reasons for changes, and distinguish variations in interventions.", "review_level": "Reuse of original bytes, SHA, and historical methodological principles preserved in 1585. This does not represent new reading of the full methodological texts, application of official methods, or certification in this review." }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish and link studies and reports, and do not omit studies solely because outcomes were unreported.", "review_level": "Reuse of original bytes, SHA, and historical methodological principles preserved in 1585. This does not represent new reading of the full methodological texts, application of official methods, or certification in this review." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement, and selective reporting.", "review_level": "Reuse of original bytes, SHA, and historical methodological principles preserved in 1585. This does not represent new reading of the full methodological texts, application of official methods, or certification in this review." }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance, and applicability. Sample size alone does not determine precision.", "review_level": "Reuse of original bytes, SHA, and historical methodological principles preserved in 1585. This does not represent new reading of the full methodological texts, application of official methods, or certification in this review." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations, and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Reuse of original bytes, SHA, and historical methodological principles preserved in 1585. This does not represent new reading of the full methodological texts, application of official methods, or certification in this review." } ], "status_dictionary": { "Met": "The question identity/record conditions were verified within the currently preserved scope. This does not establish clinical efficacy.", "Partly verified": "Some information is available, while gaps in direct conditions/material remain.", "Unverified": "The actual material and values needed for the selected condition could not be verified within the current scope.", "Not met": "The verified ingredient, endpoint, or comparison does not meet the selected direct conditions. This is not a verdict of no effect.", "Conflicting information": "A wording inconsistency preserved within the same report. This is distinguished from differences between analyses or current independent verification of the original full text.", "Not read": "The external material was not actually read in this review." }, "study_overlap": { "state": "These are the family labels and report links in the original material. The 15 citations, 9 retained evidence entries, and 14 family links are different structural counts, not counts of independent eligible direct clinical trials. F06 (S05, S31) / OFFICIAL-NIH-BIOTIN (S06) / OFFICIAL-FDA-BIOTIN (S07) / F01 (S20) / F02 (S21) / REVIEW-LIPNER-SCHER (S22) / F03 (S23) / F04 (S24) / F05 (S25) / F07 (S26) / REVIEW-CHESSA (S27) / REVIEW-ZARAA-RICHERT (S28) / F08 (S29) / F09 (S30) S05 and S31 are grouped in the same F06; the registration is not added as a separate replication. Reviews, official documents, and discovery clues have separate roles. The number of unique trials, total participants, and independent direct replications are unverified.", "unique_trial_count": null, "unique_participant_count": null, "reason": "These are the family labels and report links in the original material. The 15 citations, 9 retained evidence entries, and 14 family links are different structural counts, not counts of independent eligible direct clinical trials. F06 (S05, S31) / OFFICIAL-NIH-BIOTIN (S06) / OFFICIAL-FDA-BIOTIN (S07) / F01 (S20) / F02 (S21) / REVIEW-LIPNER-SCHER (S22) / F03 (S23) / F04 (S24) / F05 (S25) / F07 (S26) / REVIEW-CHESSA (S27) / REVIEW-ZARAA-RICHERT (S28) / F08 (S29) / F09 (S30) S05 and S31 are grouped in the same F06; the registration is not added as a separate replication. Reviews, official documents, and discovery clues have separate roles. The number of unique trials, total participants, and independent direct replications are unverified." }, "history": [ { "date": "2026-11-03", "kind": "Separation of the public interface and data", "view_version": "1.0", "change": "The public interface and data were prepared from the existing 42 items. No new clinical search, change in verification status, or scoring was performed." } ], "language": "en", "translation_date": "2026-11-03" }