{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3103-main", "verdict_number": "3103", "title": "Biotin (vitamin B7), sole-active oral product × Increased target-area non-vellus hair density in adult androgenetic alopecia, with separate sex strata", "view_version": "1.0", "view_created_date": "2026-11-02", "criteria_version": "NGM-v3103-BIOTIN-AGA-SEX-NONVELLUS-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Archived Korean and English manuscripts and case-specific condition and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No new external clinical abstracts, full texts, registrations, or analysis plans were read. Historical access records are distinguished from the archived summaries read in this review. The original assessment, numbers, and unverified matters are preserved; no new search, calculation, or reassessment was performed.", "date_meaning": "The date on which the archived material was checked, not the date of an up-to-date clinical literature search." }, "claim_context": { "population": "Adults with diagnosed androgenetic alopecia; separate male and female strata, no pooled effect; correction of objectively established deficiency and other causes of hair loss excluded", "intervention": "Biotin (biotin; vitamin B7), sole active ingredient · A sole-active oral product is the question boundary; actual tablet/capsule, batch, purity, and excipients unverified · Oral (fixed by the question; topical use and injections excluded)", "dose": "Unverified — eligible regimen dose, frequency, and total intake unverified", "comparator": "Matched-background placebo, no-treatment, and usual-care candidates kept separate; actual eligible comparator unverified", "endpoint": "Between-group difference in change in target-area non-vellus density prioritized, with between-group endpoint difference kept separate; definition, site, unit, time point, and denominator unverified", "duration": "Unverified — eligible regimen treatment duration and assessment time point unverified", "excluded_extensions": "Correction of objectively established deficiency, other causes of hair loss, topical use, injections, growth speed in healthy people, multicomponent products, combination therapy, and pooled male/female effects are excluded from this question about a single-ingredient oral product, diagnosed adult AGA, and sex-specific non-vellus density." }, "requirements": [ { "item_id": "N01", "question_type": "Identity of the claim being assessed", "question": "Which independent claim and original assessment URL are linked?", "needed": "The current original's /ko/effect, /facets, /url, and actual subclaims.", "role": "Required", "role_reason": "Needed to avoid merging other biotin assessments concerning skin, nails, or neurological disease into the same claim.", "application_exception": "The male and female strata are predefined question boundaries included in this assessment's scope. The empty subclaims in the source data do not automatically generate two new cases.", "criterion": "Link the exact wording of /ko/effect, sole-active oral biotin, diagnosed adult AGA, sex strata, non-vellus density, and matched-background comparison to a single claim.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed — an in-house adaptation for the identity of the claim being assessed; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "When assigning production, first finalize the inclusion/exclusion table for this question and determine whether a new independent claim exists through a separate boundary review.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original /ko/effect is increased target-area non-vellus density in adult AGA, with the sexes kept separate. It remains a single question about oral biotin as the sole active ingredient and a matched-background control; male and female results are not pooled. The actual subclaims are an empty array. The different questions and original URLs of 009·866·1639 are preserved.", "condition_status": "Met", "status_reason": "The exact original claim, empty subclaim structure, canonical URL, and boundaries of other related assessments were checked against the current source. This does not mean that direct efficacy has been established.", "missingness": "The identity of the original claim was verified, but the eligible preparation, dose, duration, measurements/denominators, and effect values remain unverified under separate conditions.", "uncertainty": "Separate male and female results have not been provided; the question definition alone cannot establish two efficacy findings or two independent trials.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "The current original's /ko/effect, /facets, /url, and actual subclaims." }, { "item_id": "N02", "question_type": "Scope of verification", "question": "Within what scope do ? and null values indicate unverified direct evidence?", "needed": "The evidence cutoff date, assessment gate, human_study_exists_scope, and actual record of the prior search scope.", "role": "Required", "role_reason": "Needed to prevent an unverified eligible result from being read as the absence of all human studies or as no effect.", "application_exception": "Separate the prior search cutoff date from the date of this review of preserved material. No up-to-date comprehensive search is being performed in this review.", "criterion": "Preserve the original stage0, ? and null score, together with the existence of related human studies, and specify the scope within which directly eligible results remain unverified.", "basis": "M04 §4.5, §4.6.3; limits on the current material transformation follow the user-defined scope and in-house design; M04 §4.6.3, M15 §15.3.1–15.3.3; state separation is self-designed — an in-house adaptation for the scope of verification; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Check expressions of absence in the currently preserved content by population, intervention, endpoint, and date; in any future authorized update, first verify the prior search scope.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S09", "S10", "S11", "S12" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original evidence cutoff date is 2026-09-15. The ? grade and null score mean that a directly eligible sole-active controlled result for this fixed endpoint remains unverified; they do not mean an effect of 0. The original human_study_exists_scope is preserved alongside them. Because related_human_studies_exist=true, this also does not mean that no human studies exist at all.", "condition_status": "Met", "status_reason": "The original gate and scope wording were checked together with the existence of related human studies to distinguish unverified evidence from no effect. The existing B/P classification and unscored axes are preserved citations of the original record.", "missingness": "The prior detailed search/selection log and eligible direct results are not in the current input, and no up-to-date search was performed.", "uncertainty": "This table makes no new judgement about whether studies exist outside the original search scope, the magnitude of the direct effect, or replication.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "The evidence cutoff date, assessment gate, human_study_exists_scope, and actual record of the prior search scope." }, { "item_id": "N03", "question_type": "Reading history", "question": "Is actual reading of archived summaries distinguished from historical external reading?", "needed": "The 12 citation originals, exact pointers, literals, and SHA in the currently preserved source, and the types of historical material.", "role": "Required", "role_reason": "Needed so that external URLs or historical full_text labels do not appear to indicate successful full-text reading in this review.", "application_exception": "All current external access is unattempted. Past failed-access and reading records remain only as contemporaneous reports for the respective citations.", "criterion": "Separate the source's archived summaries read in this review from each citation's historical access_level and location; retain null when a report-specific access date is absent.", "basis": "Data-collection/selection principles in M04 §4.5–4.6; the separation of access from reading and the hyperlink contract are self-designed; M04 §4.5, §4.6.3; limits on the current material transformation follow the user-defined scope and in-house design — an in-house adaptation for reading history; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Create a report-specific material ledger, linking summary reading to the actual location of the preserved archived summary and external links separately as entry points to material.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "In this review, all currently preserved archived summaries were read. Access to the PMC HTML text and tables of S03, the PDF of S05, and the official web texts of S06·S07 is reported historically in the original citations. Access to the 12 external materials was unattempted in this review, and they were neither acquired nor read. Because the original citations have no individual access dates, these remain null; the global verified_date remains a separate original review date.", "condition_status": "Partly verified", "status_reason": "Historical access levels for each material were separated from summary reading in this review, but the external documents' current public availability, original bytes, and content were not checked in this review.", "missingness": "Current external original texts/registrations, physical files, and report-specific access dates have not been acquired, and the separate source_package ZIP was not opened.", "uncertainty": "The existence of a link or a historical full_text record does not guarantee successful reading now.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "The 12 citation originals, exact pointers, literals, and SHA in the currently preserved source, and the types of historical material." }, { "item_id": "N04", "question_type": "Report lineage", "question": "How are reports, reviews, registrations, and study families linked?", "needed": "Original evidence/source_id/family_id, citation identifiers, and the S05–S11 linking statement; the actual family table if needed.", "role": "Required", "role_reason": "Needed to avoid counting repeated citations in reviews and registration documents as independent replication trials.", "application_exception": "F01–F05 in evidence are family labels in the original record. Because the separate trial_families content was not read, no new definitive unique trial or participant counts are assigned.", "criterion": "Preserve the shared registration lineage of S05 and S11; do not count reviews, safety studies, or unverified registrations as direct efficacy replications.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/result linking is an in-house application; M04 §4.6.1–4.6.2; adaptation for harms material is self-designed — an in-house adaptation for report lineage; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Create a report–registration–trial–endpoint linkage table to distinguish verified membership in the same family from unresolved links.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08", "S09", "S10", "S11", "S12" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Preserve the original evidence labels F01=S03, F02=S04, F03=S05, F04=S08, F05=S10. S11 shares the registration lineage of S05 and is not counted as independent replication. Reviews, official safety documents, and unverified registrations are not added to direct efficacy trials. The current source does not contain the detailed trial_families content.", "condition_status": "Partly verified", "status_reason": "The verified S05–S11 link and original family labels were checked, but the current input lacks the complete original data on detailed families/repeated citations; the independence of all families was therefore not established.", "missingness": "The studies-included tables from reviews, detailed family tables, registration/publication links, and unique-participant links have not been acquired.", "uncertainty": "Neither the 12 reports nor the F01–F05 labels signify 12 or 5 independent direct trials.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Original evidence/source_id/family_id, citation identifiers, and the S05–S11 linking statement; the actual family table if needed." }, { "item_id": "N05", "question_type": "Male stratum", "question": "Can between-group results for male AGA be verified separately?", "needed": "/ko/sex_strata/0 and actual tables for diagnosis, arm-specific denominators, measurement, and analysis.", "role": "Required", "role_reason": "Because the assessment distinguishes males and females, denominators and effects for the male stratum cannot be replaced with data from the female stratum or from healthy men.", "application_exception": "Growth-speed results from 10 healthy men are not direct results for male AGA. A sex-stratum definition is not presented as proof of effect modification.", "criterion": "Separately link allocation and analysis denominators, units, time points, between-group differences in change/endpoint values, and CI and P values for the male AGA stratum.", "basis": "M03 §3.2.1; detailed population conditions are self-designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are self-designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are self-designed — an in-house adaptation for the male stratum; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "If eligible material is acquired in the future, review results that match the male-stratum question by prespecified endpoint and time point.", "current_reports": [ "S03", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "In the original male stratum, between-group difference in change, between-group endpoint difference, analysis_n, unit, time, ci, and p are all null. S03's 10 healthy men are not a direct analysis population for non-vellus density in male AGA.", "condition_status": "Unverified", "status_reason": "Actual controlled results, sex-specific denominators, and time points for male AGA were not verified within the currently preserved scope.", "missingness": "Arm-specific allocation/analysis/completion denominators, density units, time points, between-group effects, CI, and P values for the diagnosed male AGA stratum are absent.", "uncertainty": "Results in healthy men cannot be applied to the stratum of men with diagnosed AGA, and null values do not mean no effect.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "/ko/sex_strata/0 and actual tables for diagnosis, arm-specific denominators, measurement, and analysis." }, { "item_id": "N06", "question_type": "Female stratum", "question": "Can between-group results for female AGA be verified separately?", "needed": "/ko/sex_strata/1 and diagnosis and arm-specific result tables for the female stratum; information on the population included in S04.", "role": "Required", "role_reason": "Needed to avoid reassigning data from women with self-reported thinning or mixed-sex data as results for the diagnosed female AGA stratum.", "application_exception": "The fact that S04 studied women does not by itself make its diagnosis, intervention, or endpoint directly eligible.", "criterion": "Separately link allocation and analysis denominators, matched-background comparison, non-vellus density results, and intervals for the female AGA stratum.", "basis": "M03 §3.2.1; detailed population conditions are self-designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are self-designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are self-designed — an in-house adaptation for the female stratum; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "If eligible material is acquired in the future, review female-stratum results separately without pooling them with the male stratum.", "current_reports": [ "S04", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "In the original female stratum, between-group difference in change, endpoint difference, analysis_n, unit, time, ci, and p are all null. S04 was excluded from the original question because it concerned self-reported hair thinning in women and a multicomponent marine-protein product.", "condition_status": "Unverified", "status_reason": "Being women in common does not make diagnosis, product, non-vellus density, or comparator the same; direct results for female AGA remain unverified.", "missingness": "Diagnosis, arm-specific denominators, time points, density measures, between-group effects, and intervals for the female AGA stratum are absent.", "uncertainty": "Results for self-reported thinning in women or for products in mixed-sex populations were not used as direct effects in female AGA.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "/ko/sex_strata/1 and diagnosis and arm-specific result tables for the female stratum; information on the population included in S04." }, { "item_id": "N07", "question_type": "Diagnosis and selection", "question": "Are AGA diagnosis and severity distinguished from cosmetic concerns in healthy people?", "needed": "Diagnostic and selection criteria, distributions of sex, age, and severity, and /actual_trial_fields/diagnosis_severity.", "role": "Required", "role_reason": "Nonpathological concerns in healthy adults or self-reported hair thinning differ from the original target population.", "application_exception": "When diagnostic criteria and severity are currently unverified, do not arbitrarily insert a specific diagnostic scale or threshold.", "criterion": "Explain actual AGA diagnosis, selection, exclusion, severity, and other causes of hair loss by reference to locations in the original text.", "basis": "M03 §3.2.1; detailed population conditions are self-designed — an in-house adaptation for diagnosis and selection; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Create a population-eligibility table and individually review the reasons for excluding healthy people in S03, self-reported concerns in S04, and nonpathological cosmetic concerns in S05.", "current_reports": [ "S03", "S04", "S05", "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original question concerns adults with diagnosed AGA. diagnosis_severity for an eligible trial is null. S03 concerns healthy men, S04 self-reported thinning, and S05 nonpathological hair, skin, and nail concerns in healthy adults; their actual diagnostic populations therefore differ.", "condition_status": "Partly verified", "status_reason": "Population differences in related material were verified, but diagnostic criteria, severity, and selection in a directly eligible AGA trial were not verified.", "missingness": "Eligible AGA diagnostic and severity criteria, selection/exclusion, age/sex composition, and information on other causes of hair loss have not been acquired.", "uncertainty": "Verifying that related populations in the current material differ does not supply AGA diagnostic criteria or establish the existence of an effect.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Diagnostic and selection criteria, distributions of sex, age, and severity, and /actual_trial_fields/diagnosis_severity." }, { "item_id": "N08", "question_type": "Baseline biotin", "question": "Is correction of objectively established deficiency distinguished from the general AGA question?", "needed": "Baseline assay method, time point, deficiency criteria, and actual individual-participant results.", "role": "Required", "role_reason": "Needed to avoid converting improvement in deficiency-related hair problems into an AGA treatment effect when deficiency status is unverified.", "application_exception": "Absent a baseline assay, do not assume either normal status or deficiency. Deficiency cases may be preserved as related material.", "criterion": "Record the extent to which baseline biotin measurement and the definition of deficiency have been verified; retain correction of objectively established deficiency as a separate question.", "basis": "M03 §3.2.1; detailed population conditions are self-designed; M04 §4.5, §4.6.3; limits on the current material transformation follow the user-defined scope and in-house design — an in-house adaptation for baseline biotin; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Review directness by baseline status and separate re-cited deficiency-correction cases from AGA controlled trials.", "current_reports": [ "S01", "S02", "S12" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "baseline_biotin_status has a null value and is not_verified. The manuscript does not treat unverified baseline biotin assays or deficiency definitions as evidence of normal status. Correction of objectively established deficiency is kept separate from the general AGA density question.", "condition_status": "Unverified", "status_reason": "The actual baseline status and definition of deficiency for the directly relevant population cannot be verified from the current source.", "missingness": "Baseline assay method, time point, definition of deficiency, and individual-participant status and results are absent.", "uncertainty": "Neither deficiency nor normal status was assumed, and deficiency cases in reviews were not reassigned as between-group effects for the original question.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Baseline assay method, time point, deficiency criteria, and actual individual-participant results." }, { "item_id": "N09", "question_type": "Sole ingredient and route", "question": "Was the actual treatment oral biotin as the sole active ingredient?", "needed": "Product ingredient list, chemical form, batch, purity, excipients, and actual administration records.", "role": "Required", "role_reason": "Needed to avoid attributing contributions from other active ingredients, botanical extracts, or topical interventions to sole-active oral biotin.", "application_exception": "The oral route is fixed in the question, but the actual eligible product's chemical form, tablet/capsule, batch, and purity remain unverified.", "criterion": "Link raw materials, ingredient list, formulation, and route to the extent verified, and separate products containing other active ingredients from direct sole-active results.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labels and assay adaptations are self-designed — an in-house adaptation for sole ingredient and route; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Use an intervention ingredient–formulation–route comparison table to review whether the product is an eligible sole-active product.", "current_reports": [ "S03", "S04", "S05", "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Oral biotin as the sole active ingredient is fixed as a boundary of the original question. Topical use and injections are excluded. exact_chemical_form and product_batch_purity for an actual eligible preparation are null, and tablet/capsule, batch, purity, and excipients are also unverified.", "condition_status": "Partly verified", "status_reason": "The route and sole-active status specified in the question were linked, but there is no material verifying the composition and formulation of an actual eligible product.", "missingness": "The exact chemical form, raw materials, ingredient list, formulation, brand, batch, purity, and excipients of an eligible product have not been acquired.", "uncertainty": "The question definition alone was not used to verify that the product actually administered was a pure sole-active preparation.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Product ingredient list, chemical form, batch, purity, excipients, and actual administration records." }, { "item_id": "N10", "question_type": "Botanical extract", "question": "What do the quantities of 250 mg extract and 1.25 mg biotin equivalent refer to?", "needed": "S05's product composition table, capsule count, administration frequency, arm-specific ingredients, and product description preserved in the manuscript.", "role": "Required", "role_reason": "Needed to avoid equating an extract name or biotin equivalent with an amount of pure biotin as the sole active ingredient.", "application_exception": "Do not automatically convert the per-capsule amount to a daily total. Do not merge the silica-containing arm with the same sole-active product.", "criterion": "Distinguish S05's Sesbania extract, biotin equivalent, and other extract constituents, and preserve the limits on effect attribution.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labels and assay adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; in-house application — an in-house adaptation for botanical extract; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Separate the differences in active ingredients across S05 arms to distinguish sole-active biotin comparisons from combination/extract comparisons.", "current_reports": [ "S05", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The biotin-labelled arm in S05 used Sesbania grandiflora extract; the manuscript reports 250 mg extract and 1.25 mg biotin equivalent per capsule. The silica-extract arm is also a separate intervention. These values do not constitute an established effective sole-active biotin regimen.", "condition_status": "Met", "status_reason": "The product amounts, ingredient attribution, and limits on sole-ingredient interpretation in the current manuscript were checked. Positive product findings were not deleted.", "missingness": "The regimen and total exposure for an eligible sole-active product remain unverified, and S05's detailed capsule count and original composition table were not externally checked in this review.", "uncertainty": "The 250 mg extract amount was not converted into a biotin amount, nor was the per-capsule equivalent converted into a daily total.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "S05's product composition table, capsule count, administration frequency, arm-specific ingredients, and product description preserved in the manuscript." }, { "item_id": "N11", "question_type": "Dose and total exposure", "question": "Have eligible dose, frequency, and total dietary and concurrent supplement exposure been verified?", "needed": "Medication-taking/adherence records, dietary/concurrent supplement amounts, dose tables, and /actual_trial_fields/dose_frequency and total_exposure.", "role": "Required", "role_reason": "Needed to avoid reassigning the 5 mg/day or extract-per-capsule amounts from related trials as a verified regimen for the original question.", "application_exception": "This table does not determine an optimal dose. Missing dietary or other supplement amounts do not justify equating total intake with the administered dose.", "criterion": "Separate an eligible product's actual administered dose, frequency, and total exposure from the nominal amounts in related studies.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labels and assay adaptations are self-designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are self-designed — an in-house adaptation for dose and total exposure; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In an authorized follow-up review, check exposure records by arm; review the optimal-dose question separately only when a direct dose comparison exists.", "current_reports": [ "S03", "S05", "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Eligible dose_frequency and total_exposure are null and not_verified. S03's 5 mg/day is the amount for a crossover period assessing growth speed in healthy people, and S05's per-capsule amount refers to a different product.", "condition_status": "Unverified", "status_reason": "The actual amount, frequency, and total dietary/concurrent supplement amounts for an eligible sole-active regimen were not verified from the current source.", "missingness": "Administration frequency, medication-taking/adherence, dietary amounts, and concurrent supplement amounts for a directly eligible product have not been acquired.", "uncertainty": "Amounts in related studies cannot be used to specify an effective or optimal dose for the original question.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Medication-taking/adherence records, dietary/concurrent supplement amounts, dose tables, and /actual_trial_fields/dose_frequency and total_exposure." }, { "item_id": "N12", "question_type": "Comparator and concomitant treatment", "question": "Have a matched-background control group and concomitant treatments actually been verified?", "needed": "Arm-specific background treatment, adherence/rescue records, control-preparation ingredients, and the actual analysis plan.", "role": "Required", "role_reason": "Needed to prevent differences in minoxidil or product ingredients from being mixed with the contribution of the selected intervention.", "application_exception": "Placebo, no treatment, and usual care are candidate comparators in the question; this does not mean that the control group of an actual eligible trial has been verified.", "criterion": "Distinguish actual control content, shared treatments, rescue treatment, adherence, and analytical handling from the contribution of sole-active biotin.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labels and assay adaptations are self-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; in-house application — an in-house adaptation for comparator and concomitant treatment; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Create an arm-specific intervention matrix to separate sole-active biotin contrasts from combination-intervention contrasts.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original comparator lists matched-background placebo, no-treatment, and usual-care candidates separately. Eligible background_treatment is null. The minoxidil+biotin in S03 and the extract combination in S05 do not substitute for a matched-background control for sole-active biotin.", "condition_status": "Unverified", "status_reason": "There is no material verifying the actual eligible control group, shared treatment, or differences in rescue treatment/adherence.", "missingness": "Information on arm-specific control preparations, shared/concurrent treatments, adherence, rescue treatment, and analytical handling has not been acquired.", "uncertainty": "The proposed comparator candidates were not presented as actually verified control groups, and results from combination periods were not attributed to the sole ingredient's contribution.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Arm-specific background treatment, adherence/rescue records, control-preparation ingredients, and the actual analysis plan." }, { "item_id": "N13", "question_type": "Duration and time point", "question": "What are the eligible treatment duration and assessment time point?", "needed": "Administration/assessment visit schedule, endpoint-specific result time points, and /actual_trial_fields/duration.", "role": "Required", "role_reason": "Needed to avoid converting related study durations of 14 days and 90 days into eligible durations for AGA non-vellus density.", "application_exception": "Do not introduce new numbers for the hair cycle or minimum observation period. Long-term maintenance effects are a separate extension question.", "criterion": "Attribute treatment start, assessment time point, and observation period to the same endpoint and analysis, and retain the unverified status of the eligible duration.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are self-designed; M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are self-designed — an in-house adaptation for duration and time point; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Link report-specific timelines during production; review any future persistence question only using direct long-term or post-discontinuation material.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Eligible duration is null and not_verified. S03 reports 14 days per regimen, and S05 reports 90 days as related study durations. These durations were not adopted as eligible treatment durations or optimal assessment time points for non-vellus density in male or female AGA.", "condition_status": "Unverified", "status_reason": "Actual duration and assessment time point linked to the directly relevant population, product, and endpoint were not verified.", "missingness": "Eligible administration start/end, visit schedule, result time points, and follow-up duration are absent.", "uncertainty": "No arbitrary numbers were assigned to the hair cycle, minimum time to effect, or maintenance period.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Administration/assessment visit schedule, endpoint-specific result time points, and /actual_trial_fields/duration." }, { "item_id": "N14", "question_type": "Definition of non-vellus hair", "question": "Is non-vellus density distinguished from hair count, thickness, shedding, and growth speed?", "needed": "Definition of non-vellus hair, scope of density calculation, units, measurement manual, and original result tables.", "role": "Required", "role_reason": "Needed to avoid replacing the original endpoint's definition and units with other hair measures.", "application_exception": "Because the criteria for hair miniaturization and distinction of non-vellus hair are currently unverified, do not arbitrarily fill in a specific diameter threshold.", "criterion": "Link the criteria for distinguishing non-vellus hair, density units, and direction, while retaining growth speed in mm/week, hair thickness, photographs, and satisfaction as separate outcomes.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to the question is locally designed; M08 Table 8.2.a, M03 §3.2.4; local application — local adaptation of the non-vellus definition; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compile an endpoint dictionary and check whether each hair outcome directly matches the original question.", "current_reports": [ "S03", "S04", "S05", "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original primary_endpoint prioritizes the between-group difference in change in target-area non-vellus density and treats the difference in endpoint values separately. assay_definition is null, and the non-vellus criteria, scalp site, measurement method, unit, direction, and time point remain unverified. Growth speed in mm/week, hair count, thickness, photographs, and satisfaction are separate outcomes.", "condition_status": "Unverified", "status_reason": "The original endpoint name is fixed, but the actual definitions for distinguishing non-vellus hair and measuring density have not been verified.", "missingness": "The non-vellus diameter criterion, density unit, calculation scope, measurement/reading procedures, and results tables are unavailable.", "uncertainty": "Reduced hair shedding, miniaturization, or other hair measures were not automatically substituted for an increase in non-vellus density.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Definition of non-vellus hair, scope of density calculation, units, measurement manual, and original result tables." }, { "item_id": "N15", "question_type": "Target area and measurement", "question": "Was the same scalp target area assessed under the same measurement conditions?", "needed": "Target-area selection, area size, photography/measurement, reading, blinding, and repeat-visit procedures.", "role": "Required", "role_reason": "Needed to avoid interpreting differences in site, area size, photography, or reading as an increase in non-vellus hair.", "application_exception": "Do not reclassify the original P as a surrogate endpoint solely because an assessor performs the measurement. Inability to blind does not automatically constitute failure either.", "criterion": "Record the target area, repeated measurements, assessment procedures, blinding, and differences in conditions between groups, limited to what has been verified.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to the question is locally designed; M08 Table 8.2.a, M03 §3.2.4; local application — local adaptation of target-area assessment and measurement; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In future eligible reports, compare the same site, measurement time points, and reading conditions to establish the scope within which measurements can be interpreted.", "current_reports": [ "S03", "S04", "S05", "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The eligible scalp target area, repeated measurements, and reading/blinding conditions remain unverified in assay_definition. The manuscript's P classification means that hair restoration itself is the treatment target; it does not establish measurement reliability or clinical importance.", "condition_status": "Unverified", "status_reason": "There are no direct data for comparing the same site, area size, measurement procedures, and measurement differences between groups.", "missingness": "Data on target-area selection, area size, repeated photography/measurement, reading, blinding, and measurement error have not been acquired.", "uncertainty": "No new judgement that the outcome is problem-free or a surrogate endpoint was made solely because the measurement is objective.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Target-area selection, area size, photography/measurement, reading, blinding, and repeat-visit procedures." }, { "item_id": "N16", "question_type": "Effect of interest", "question": "Are the between-group change difference and the between-group endpoint difference distinguished?", "needed": "Baseline/endpoint values and changes by group, the analysis population, and the definition of the effect of interest and adjustment plan.", "role": "Required", "role_reason": "Needed to avoid treating within-group pre/post changes or endpoint values as the same between-group effect on change.", "application_exception": "If the original report does not specify the analysis population or adjustments, do not arbitrarily label the result ITT, PP, or an adjusted effect.", "criterion": "Preserve the original question's structure of prioritizing the between-group change difference and treating the endpoint difference separately, and link sex, time point, and analysis definition.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to the question is locally designed; M08 §8.2.2, M15 §15.3.1; local application — local adaptation of the effect of interest; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Link each result's endpoint–time point–analysis–effect of interest in a table to distinguish between-group from within-group estimates.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "between_group_change_difference and between_group_endpoint_difference in the original male and female strata are each null. The original question prioritizes the between-group change difference while retaining the between-group endpoint difference separately. The within-group pre/post P values in S03 do not replace these two between-group results.", "condition_status": "Unverified", "status_reason": "The selected between-group effect of interest and the actual analysis population, adjustments, and result values have not been verified.", "missingness": "Group-specific baseline/endpoint/change values, ITT/PP status, adjustments, sex-specific analysis definitions, and between-group estimates are unavailable.", "uncertainty": "No analysis label or between-group difference in change was arbitrarily created.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Baseline/endpoint values and changes by group, the analysis population, and the definition of the effect of interest and adjustment plan." }, { "item_id": "N17", "question_type": "Allocation design", "question": "Can the actual allocation, concealment, and baseline balance for the selected result be verified?", "needed": "Linkage of methods, allocation/concealment procedures, and the baseline table to the original endpoint result.", "role": "Required", "role_reason": "Needed to avoid claiming that a causal comparison for the original question is established solely from an RCT label in a nearby study.", "application_exception": "The randomized-sequence crossover in S03 and the double-blind design in S05 with 3 arms are characteristics of those studies; they do not establish direct eligibility.", "criterion": "Show the design, allocation, concealment, and baseline information linked to an eligible result, retaining what is actually unverified.", "basis": "M08 §8.1–8.2.3; local application — local adaptation of allocation design; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compare design eligibility and actual allocation processes for each report, separating population, intervention, and endpoint mismatches from design limitations.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S03 is recorded in the original evidence as an open randomized-sequence self-controlled crossover, and S05 as a randomized double-blind placebo-controlled three-arm single-center trial. Because both studies are not directly eligible owing to population, product, and endpoint mismatches, they do not substitute for verification of allocation/concealment for the original question.", "condition_status": "Unverified", "status_reason": "No data on allocation, concealment, or baseline balance are linked to a directly eligible result.", "missingness": "Methods, allocation/concealment procedures, and baseline tables for an eligible comparison of biotin alone in AGA have not been acquired.", "uncertainty": "A nearby study's being recorded as an RCT was not elevated into established causal efficacy for the original question.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Linkage of methods, allocation/concealment procedures, and the baseline table to the original endpoint result." }, { "item_id": "N18", "question_type": "Crossover analysis", "question": "Which comparisons can the crossover and within-group results in S03 address?", "needed": "S03 crossover sequence, analyses by period, handling of carryover/sequence, paired variance, and the actual tables.", "role": "Required", "role_reason": "Needed to avoid counting regimen periods experienced by the same 10 participants as separate participant groups or independent replications.", "application_exception": "Do not newly fill in details of sequence, washout period, carryover effects, or paired variance that are unverified in the original retained archived summaries.", "criterion": "Retain the crossover periods in 10 healthy men and the within-group pre/post P values, without repurposing them as a placebo-adjusted between-group effect or AGA density result.", "basis": "M08 §8.1–8.2.3; local application; M08 §8.2.2, M15 §15.3.1; local application; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation to the design is locally designed — local adaptation of crossover analysis; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In a future authorized review of the original report, verify the unit of crossover analysis, without calculating a new effect from the currently retained values.", "current_reports": [ "S03" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S03 involved 10 healthy men participating in a crossover trial in which they experienced each regimen, including biotin 5 mg/day, for 14 days. Do not convert the within-group pre/post growth-speed result into a placebo-adjusted between-group effect in separate groups or non-vellus density in male AGA.", "condition_status": "Partly verified", "status_reason": "The original crossover context and scope of analysis were verified, but the detailed original text on sequence, washout/carryover, handling of periods, and paired variance was not checked on this occasion.", "missingness": "Details of crossover sequence/washout, carryover effects, analyses by period, paired variance, and the actual tables have not been acquired.", "uncertainty": "The same 10 participants were not added up across regimen periods, nor was the number of periods converted into a count of independent replications.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "S03 crossover sequence, analyses by period, handling of carryover/sequence, paired variance, and the actual tables." }, { "item_id": "N19", "question_type": "Sex-specific analysis denominators", "question": "Are allocation, analysis, and completion denominators linked by sex and group?", "needed": "Sex- and group-specific flow diagrams, analysis N in the results tables, and records of exclusions and missing-data handling.", "role": "Required", "role_reason": "Needed to avoid filling null sex-specific results with the total number allocated in another study.", "application_exception": "The male and female strata defined by the question do not represent actual trial recruitment or analysis denominators.", "criterion": "Link the sex- and group-specific allocation/measurement/completion/analysis denominators and missing-data handling to the same outcome time point.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation to the design is locally designed; M08 §8.2.2, M15 §15.3.1; local application — local adaptation of sex-specific analysis denominators; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In future eligible data, compare the recruitment→allocation→measurement→analysis flow by sex.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "denominators has value null and status not_verified, and male and female analysis_n are also null. The actual sex- and group-specific allocation, analysis, and completion denominators cannot be verified in the current source. The male and female target strata specified in the question are not trial recruitment denominators.", "condition_status": "Unverified", "status_reason": "Sex/group-specific flow and missing-data handling attributable to the same outcome and time point remain unverified.", "missingness": "Sex- and group-specific allocation/measurement/completion/analysis N, exclusions, and missing-data handling data are unavailable.", "uncertainty": "The 10 healthy participants or the S05 totals of 105/97 participants were not substituted for eligible sex-specific analysis N.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Sex- and group-specific flow diagrams, analysis N in the results tables, and records of exclusions and missing-data handling." }, { "item_id": "N20", "question_type": "Attribution of 105·97", "question": "In S05, what are the denominators represented by the 105 allocated and 97 completed?", "needed": "S05 flow diagram by group, completion/analysis denominators, reasons for withdrawal, and results tables.", "role": "Required", "role_reason": "Needed to avoid transferring the overall participant flow in a study of healthy people with cosmetic concerns to sex-specific AGA non-vellus analysis denominators.", "application_exception": "Do not calculate reasons for withdrawal, group-specific denominators, analysis methods, or event rates from the currently available 105 and 97 alone.", "criterion": "Retain 105 allocated, 97 completed, and 90 days as the record for S05, while distinguishing the unverified group-specific, sex-specific, and selected-endpoint analysis denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation to the design is locally designed; M03 §3.2.1; detailed population criteria are locally designed — local adaptation of the attribution of 105·97; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compare participant flow and actual analysis populations in S05, recording reasons for exclusion from the direct population, intervention, and endpoint separately from missing-data limitations.", "current_reports": [ "S05", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S05 reports 105 allocated, 97 completed, and 90 days in healthy adults with nonpathological cosmetic concerns. These are values for the overall participant flow, not group-specific analysis N for non-vellus density in male and female AGA. The n field in the original evidence refers to separate trial_families/numeric_evidence.", "condition_status": "Partly verified", "status_reason": "The overall flow values have been retained, but analysis denominators by group, sex, and endpoint and reasons for missingness/withdrawal have not been verified in this input.", "missingness": "S05 allocation, completion, and analysis N by group, reasons for withdrawal, missing-data handling, and the separate referenced tables have not been acquired.", "uncertainty": "No new withdrawal count, withdrawal rate, missing-data method, or effect for the original AGA question was calculated from 105 and 97.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "S05 flow diagram by group, completion/analysis denominators, reasons for withdrawal, and results tables." }, { "item_id": "N21", "question_type": "Within-group values and variance", "question": "Are 2.50·2.47 and SD·P=0.53 attributed to the correct result?", "needed": "The original S03 table, each variance notation, analyses/footnotes, and exact quotation in the current KO.", "role": "Required", "role_reason": "Needed to avoid converting SD into SE or CI, or interpreting nonsignificance as an effect of 0 or equivalence.", "application_exception": "Do not calculate a new difference in change or CI; these numbers are not effect inputs for sex-specific AGA non-vellus density.", "criterion": "Link 2.50(SD 0.38)→2.47(SD 0.42) mm/week and within-group pre/post P=0.53 to the corresponding S03 period without alteration.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to the question is locally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is locally designed; M08 §8.2.2, M15 §15.3.1; local application; M15 §15.3.1–15.3.3; local application — local adaptation of within-group values and variance; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Verify result attribution by comparing numbers, units, variance, and comparison direction, and record that no calculation was performed.", "current_reports": [ "S03" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Growth speed during the S03 biotin period was 2.50(SD 0.38) before and 2.47(SD 0.42) mm/week after treatment, with within-group pre/post P=0.53. Retain the nonsignificant result for biotin alone on growth speed in healthy participants, without using it as a between-group non-vellus effect in male or female AGA.", "condition_status": "Met", "status_reason": "The original numbers, SD notation, units, within-group comparison direction, and reasons for exclusion in the current KO were checked. SD was not converted into SE/CI.", "missingness": "A direct between-group AGA effect and CI, and paired variance/detailed analysis for S03, have not currently been acquired.", "uncertainty": "P=0.53 is not evidence of an effect of 0 or equivalence, and no new difference in change or CI was produced.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "The original S03 table, each variance notation, analyses/footnotes, and exact quotation in the current KO." }, { "item_id": "N22", "question_type": "Positive combination result", "question": "What does the difference between within-group P=0.02 and P=0.53 for biotin alone mean?", "needed": "S03 results by regimen and the original report of any direct between-regimen/interaction analysis, if available.", "role": "Required", "role_reason": "Needed to avoid generating a between-group difference, synergy, or efficacy of biotin alone from different P values alone.", "application_exception": "Do not delete the positive growth-speed result for minoxidil+biotin. Without a direct interaction estimate, do not describe it as synergy.", "criterion": "Attribute within-group P=0.02 in the combination period and within-group P=0.53 in the biotin-alone period to their respective regimens and endpoints.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is locally designed; M03 §3.2.3, M08 §8.2.2–8.2.3; local application; M08 §8.2.2, M15 §15.3.1; local application — local adaptation of the positive combination result; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Check the identities of within-group, between-group, and interaction tests, and distinguish the scope of interpretation of each result.", "current_reports": [ "S03" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The minoxidil+biotin period in the same S03 crossover trial reports within-group growth-speed P=0.02. Link this and within-group P=0.53 in the biotin-alone period to their respective periods. A difference between P values alone does not establish a between-group difference, synergy, or an effect of biotin alone.", "condition_status": "Met", "status_reason": "Both the original positive combination result and the nonsignificant result for biotin alone were retained, with analysis and intervention attribution kept separate.", "missingness": "Direct between-regimen differences, interaction estimates, CIs, and results of a comparison of biotin alone for AGA non-vellus density have not been acquired.", "uncertainty": "The P value for the positive combination result does not meet the requirements of this question about biotin alone.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "S03 results by regimen and the original report of any direct between-regimen/interaction analysis, if available." }, { "item_id": "N23", "question_type": "Other positive results", "question": "For what reasons are the hair improvements in S04·S05 separated from direct results?", "needed": "Original product, population, and endpoint tables for S04/S05 and the scope of the historical extracts.", "role": "Required", "role_reason": "Needed to preserve positive results without repurposing results for other products, populations, or endpoints as the effect addressed by the original question.", "application_exception": "Do not introduce old numerical estimates absent from the retained source. Exclusion does not mean a finding of no effect or low quality for that study.", "criterion": "Retain the results for the multicomponent marine-protein product in self-reported thinning and for botanical extracts in nonpathological cosmetic concerns, each in its original context.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is locally designed; M03 §3.2.1; detailed population criteria are locally designed; M03 §3.2.2–3.2.3; reverse-direction labels and test adaptations are locally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; outcome adaptation to the question is locally designed — local adaptation of other positive results; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compile an eligibility matrix by report to review positive/no-difference direction separately from population, intervention, and endpoint alignment.", "current_reports": [ "S04", "S05", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S04 is excluded for its multicomponent marine-protein product and self-reported thinning, and previous numerical efficacy estimates were not imported. S05 is excluded for its botanical extract, healthy participants with nonpathological cosmetic concerns, and unverified non-vellus definition, while its positive hair-related results are retained.", "condition_status": "Partly verified", "status_reason": "Differences in directness and the existence of positive results were verified, but the current external original texts, old detailed extracted values for S04, and full results tables for S05 were not checked on this occasion.", "missingness": "Detailed original population, ingredient, and endpoint tables for S04/S05 and numerical values not currently retained have not been acquired.", "uncertainty": "Positive results for other products/populations/endpoints were not concealed, and exclusion was not expressed as a finding of no effect or a new quality grade for those studies.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Original product, population, and endpoint tables for S04/S05 and the scope of the historical extracts." }, { "item_id": "N24", "question_type": "Intervals and clinical importance", "question": "Can direct between-group CIs and criteria for clinical importance be verified?", "needed": "Between-group effects/variance/CIs, analysis denominators, and evidence for clinical importance in the relevant population and endpoint.", "role": "Required", "role_reason": "Needed to avoid filling in precision or a sufficient effect solely from P values, total sample size, or the number of trials.", "application_exception": "Do not arbitrarily set an MCID or common threshold for sample size or duration. The original P classification is separate from verification of a criterion for clinical importance.", "criterion": "Link between-group effects and CIs by sex, endpoint, and time point to a justified important difference, retaining the reasons for the current null values.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation to the design is locally designed; M15 §15.3.1–15.3.3; local application — local adaptation of intervals and clinical importance; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In future, compare directly reported values with the stated basis for clinical importance to explain the range of effects compatible with the evidence, without creating new grades or calculated values.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "actual_trial_fields/effect and mcid are null and not_verified, and male and female ci/p are also null. SD or within-group P from S03, or total N from S05, does not replace sex-specific AGA between-group CIs, precision, or an important difference.", "condition_status": "Unverified", "status_reason": "The interval for a direct between-group estimate and the criterion for clinical importance in the relevant population, endpoint, and time point cannot be verified.", "missingness": "Sex-specific between-group effects, CIs, variance, analysis N, and evidence supporting a justified important difference are unavailable.", "uncertainty": "No sufficiency judgement or new precision/efficacy grade was created solely from sample size, significance, or the number of trials.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Between-group effects/variance/CIs, analysis denominators, and evidence for clinical importance in the relevant population and endpoint." }, { "item_id": "N25", "question_type": "Plan and registration linkage", "question": "Were the planned endpoints and analyses compared between the S05 article and the S11 registration?", "needed": "S05 plans, protocol/SAP, original registration text and amendment history, and planned endpoint hierarchy.", "role": "Required", "role_reason": "Needed to avoid assigning the same status to a registration identifier printed in an article and a completed check against the registration history.", "application_exception": "Do not convert failure to acquire the registration text or history into a conclusion of nonregistration or confirmed selective reporting. S11 is not a new replication trial.", "criterion": "Distinguish the identifiers reported by S05, NCT05972512/CTRI, from the actual scope of verification of the official registration.", "basis": "M08 Table 8.2.a, M04 §4.6.3; local application; the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application; M04 §4.5, §4.6.3; limits on the current data transformation reflect the user's scope and local design — local adaptation of plan and registration linkage; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "If materials become available in future, compare planned endpoints, time points, and analyses against results within the same family.", "current_reports": [ "S05", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S05 reports NCT05972512 and CTRI/2023/11/055359 in the article. S11 is grouped within the same S05 lineage, but the registration content and history were not acquired, and the planned endpoint hierarchy was not independently verified. Verification of the DOI in the PDF at that time and verification of the registration history are different statuses.", "condition_status": "Unverified", "status_reason": "The presence of a registration identifier alone did not complete the comparison of the protocol, SAP, prospective analyses/endpoints, and time points.", "missingness": "The official registration text/amendment history, protocol/SAP, and comparison of planned endpoints/analyses with results have not been acquired.", "uncertainty": "Failure to acquire the materials was not converted into nonregistration or confirmed selective reporting, and S11 was not counted as a new replication trial.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "S05 plans, protocol/SAP, original registration text and amendment history, and planned endpoint hierarchy." }, { "item_id": "N26", "question_type": "Unverified registration lead", "question": "To what extent have eligibility, product, and results been verified for S10?", "needed": "Official registration text, protocol, results/publication linkage, and product ingredients.", "role": "Required", "role_reason": "Needed to avoid filling in a registration shell/indexed title as a result for biotin alone on AGA non-vellus density.", "application_exception": "Incomplete access is not evidence of no results, trial termination, or a negative result. Do not use commercial summaries as official registration facts.", "criterion": "Distinguish a lead indicating the existence of NCT06605768 from the unverified actual sole-active status of the product, AGA eligibility, endpoint, and results.", "basis": "M04 §4.5, §4.6.3; limits on the current data transformation reflect the user's scope and local design; M08 Table 8.2.a, M04 §4.6.3; local application; the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application — local adaptation of the unverified registration lead; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "When acquisition of materials is authorized, check the identities of the official record and published results before reviewing eligibility again.", "current_reports": [ "S10" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "S10 is a lead consisting of the indexed title and registration shell for NCT06605768. Access to the official current protocol/results was incomplete at that time, and whether the product has a single active ingredient, AGA eligibility, and the non-vellus endpoint remain unverified. Commercial summaries were not adopted as official trial facts.", "condition_status": "Unverified", "status_reason": "The current input contains no complete official record with which to verify direct eligibility, product, endpoint, or results.", "missingness": "The official registration text, product ingredients, population, endpoint, and linkage to published results for S10 have not been acquired.", "uncertainty": "Incomplete access does not mean that there are no study results, that results are negative, or that the trial was terminated. No new access was attempted on this occasion either.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Official registration text, protocol, results/publication linkage, and product ingredients." }, { "item_id": "N27", "question_type": "Missing data and reporting scope", "question": "Are missing analysis data distinguished from unacquired results and plans?", "needed": "Sex- and group-specific reasons for missing data and their handling, analysis plans, original results tables, and actual copies of separately referenced files if provided.", "role": "Required", "role_reason": "Needed to avoid extending gaps in the current manuscript into claims of complete nonreporting in the article or results of 0.", "application_exception": "The separate numerical, family, and selection files referenced by the original evidence are outside this reading scope; do not claim that their contents were also read.", "criterion": "Show the denominator, missing-data, and analysis information verified in the source actually read, and separately state the scope of materials not checked.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation to the design is locally designed; M04 §4.5, §4.6.3; limits on the current data transformation reflect the user's scope and local design; M08 §8.2.2, M15 §15.3.1; local application; M08 Table 8.2.a, M04 §4.6.3; local application — local adaptation of missing data and reporting scope; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Create a map distinguishing reporting, analysis, and access gaps to identify the additional materials needed for each condition.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "Sex-specific analysis denominators and missing-data handling remain unverified in the current source. n in evidence refers to separate trial_families/numeric_evidence, and the assessment notes refer to claim_boundary/selection_log. Those separate texts and the ZIP were not opened on this occasion.", "condition_status": "Unverified", "status_reason": "The retained material read did not contain actual missing-data/analysis and selection plans or detailed referenced tables, so reporting/analysis gaps could not be checked.", "missingness": "Sex- and group-specific reasons for missing data and their handling, analysis plans, original tables, and the actual referenced files have not been acquired.", "uncertainty": "The absence of information in the current input was not extended into claims of complete nonreporting in the article, 0 events, or confirmed selective reporting.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Sex- and group-specific reasons for missing data and their handling, analysis plans, original results tables, and actual copies of separately referenced files if provided." }, { "item_id": "N28", "question_type": "Funding and employment", "question": "What is the verified scope of declared interests and independent funding?", "needed": "Original funding/disclosure text by report, product provision, author employment/institutions, and contract scope.", "role": "Supplementary; required for a claim of independence", "role_reason": "Needed to avoid turning unverified interests into proof of independent funding, or manufacturer employment into automatically invalid results.", "application_exception": "When directly eligible results remain unverified, do not fill the original independence axis solely from funding of nearby trials.", "criterion": "Link the distinct scopes of none declared in S03, historical manufacturer support in S04, and manufacturer/CRO employment and unverified contracts in S05.", "basis": "Chamgap's own independence and attribution criteria. The official methodology sections used in this pilot do not endorse all these detailed items — local adaptation of funding and employment; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compare in a table that distinguishes the level of disclosure from actual funding and family independence.", "current_reports": [ "S03", "S04", "S05" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original S03 records none declared; S04 records manufacturer support in the inherited extraction, without a new adjudication. S05 discloses employment relationships with the product manufacturer and CRO, while the full sponsorship contract remains unverified. The original direct-efficacy independence axis is null.", "condition_status": "Partly verified", "status_reason": "Disclosure, employment, and historical-extract levels were linked, but the original contracts, all provision/funding sources, and family independence were not checked against external materials on this occasion.", "missingness": "Sponsorship contracts, product provision, author/institution relationships, full disclosures, and data on the independence of directly eligible families have not been acquired.", "uncertainty": "Interests were not interpreted as automatic bias/invalidity, nor was none declared interpreted as the absence of all interests or proof of independent funding.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Original funding/disclosure text by report, product provision, author employment/institutions, and contract scope." }, { "item_id": "N29", "question_type": "Replication boundary", "question": "Can independent replication of directly eligible results be verified?", "needed": "Eligible family tables, report/registration linkage, sex-specific results, and differences in institutions, populations, and products.", "role": "Required", "role_reason": "Needed to avoid counting nearby studies in healthy participants, multicomponent-product studies, and reviews as repeated confirmation or refutation in male and female AGA.", "application_exception": "Unverified families or unverified eligible results are not automatically treated as Not applicable for comparisons across studies.", "criterion": "Explain differences in distinct families, results and conditions for the same question within the verified scope, and retain the original null values for replication/independence.", "basis": "M04 §4.6.1–4.6.2 distinguishes studies from reports; cohort/outcome linkage is an in-house application; M04 §4.6.1–4.6.2, M15 §15.3.1; in-house application — an in-house adaptation of replication boundaries; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "If eligible reports become available in the future, group repeated citations from the same family and compare results and conditions across independent families.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S09", "S10", "S11", "S12" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "At the original gate of no verified directly eligible result, replication/independence are null. Related human studies exist, but healthy-person studies, combination products, safety studies and review/registration leads do not replace independent replication of the original male and female AGA density result. S05 and S11 are the same family.", "condition_status": "Unverified", "status_reason": "Differences in direct results and conditions across distinct families matching the same original question could not be verified.", "missingness": "An eligible family table, direct results by sex, information on the same/different institutions, products and populations, and independent replication data have not been obtained.", "uncertainty": "Unresolved families or gaps in direct results were not converted into Not applicable for comparisons across studies or into repeated refutation.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Eligible family tables, report/registration linkage, sex-specific results, and differences in institutions, populations, and products." }, { "item_id": "N30", "question_type": "Extended questions", "question": "Does the original question also require optimal dose, maintenance and effects after discontinuation?", "needed": "When an extended claim is made, direct dose comparisons, discontinuation/long-term follow-up and a prespecified subgroup plan.", "role": "Supplementary; required for extended claims", "role_reason": "Needed to avoid automatically extending a specific question about change in non-vellus density to optimal dose and long-term maintenance effects.", "application_exception": "The narrow assessment target does not require every dose and duration study as a prerequisite. Verification of the basic administered dose and duration remains a separate requirement.", "criterion": "Distinguish basic actual exposure/time points from extended questions about optimal dose, effects after discontinuation and long-term maintenance.", "basis": "M03 §3.2.1–3.2.4; details of dose, duration and effect modification are designed in-house — an in-house adaptation of extended questions; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "When an extended question is actually requested, review the corresponding comparison/follow-up design separately, and do not set the required duration/number of participants without evidence.", "current_reports": [ "S03", "S05", "S10", "S11" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The current assessment target is the monotherapy comparison of AGA non-vellus density by sex, and it makes no claim about optimal dose, effects after discontinuation or long-term maintenance effects. These extension studies are not imposed as prerequisites for verifying the original result. Basic actual dose and duration remain Unverified in N11/N13.", "condition_status": "Not applicable", "status_reason": "The reason for not applying extended efficacy outside the narrow assessment target as a requirement in this table is clear.", "missingness": "There is currently no extended claim itself. Gaps in the data on eligible basic administered dose, duration and results are retained in separate rows.", "uncertainty": "Not applicable does not mean that the basic regimen or long-term effects have been verified.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "When an extended claim is made, direct dose comparisons, discontinuation/long-term follow-up and a prespecified subgroup plan." }, { "item_id": "N31", "question_type": "Endpoint extension", "question": "Are density results extended to quality of life, satisfaction or other clinical events?", "needed": "When an extended question actually exists, data on the corresponding clinical/quality-of-life endpoints and their importance.", "role": "Supplementary; not applicable to imposing an event extension at present", "role_reason": "Needed to distinguish the manuscript's treatment target of hair restoration from separate questions about quality of life and events.", "application_exception": "The original question concerns increased density, and clinical event/mortality trials are not imposed as prerequisites for verifying that result. The original P is not newly changed to S.", "criterion": "Separate non-vellus density from photographs, satisfaction, quality of life and other events, and require separate direct data if an extended conclusion is made.", "basis": "M03 §3.2.4; in-house extension boundaries; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is designed in-house — an in-house adaptation of endpoint extension; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "During preparation, check endpoint interpretation and state explicitly that no extension beyond the original boundaries is made.", "current_reports": [ "S03", "S04", "S05" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The manuscript classifies hair restoration itself as treatment target P and asks about increased non-vellus density. It does not automatically claim improvements in quality of life, satisfaction or other clinical events/mortality, and does not impose event trials as prerequisites for verifying this density result.", "condition_status": "Not applicable", "status_reason": "Although an obligation to extend to events outside the current scope is not applied, the interpretive boundary against substituting other hair/subjective outcomes is retained.", "missingness": "There is currently no separate efficacy claim concerning events or quality of life. Gaps in density definition, between-group results and clinical importance remain in separate rows.", "uncertainty": "The original P was not reclassified as S, and satisfaction/photograph results were not used to fill in the density effect.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "When an extended question actually exists, data on the corresponding clinical/quality-of-life endpoints and their importance." }, { "item_id": "N32", "question_type": "Assay interference", "question": "Which assays reported interference, and in which direction?", "needed": "Assay/version, specimen, direction of interference and actual exposure records in official documents; the corresponding scope if the S08 original is provided.", "role": "Supplementary; required to explain the safety scope", "role_reason": "Needed to retain hair-loss efficacy results and signals of falsely high/low results in selected assays as distinct states.", "application_exception": "Limit this to susceptible assays such as troponin, TSH and NT-proBNP, without extending it to interference in all assays or causation of clinical events.", "criterion": "Distinguish the retained NIH/FDA statements and the historical safety context of S08 by assay, direction and exposure scope.", "basis": "M19 §19.1.2–19.2.4; in-house application; M19 §19.1.2–19.2.4; detailed distinctions are designed in-house; design considerations in M19 §19.2.2–19.2.4; detailed confounding records are designed in-house; Chamgap's own interpretation boundary. Reference to M19 principles, not execution of an official causality tool — an in-house adaptation of assay interference; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "In the assay–exposure–direction map, distinguish official warnings from repeat citations of original studies, without creating personal testing/dosing instructions.", "current_reports": [ "S06", "S07", "S08" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original safety statement reports biotin interference causing falsely high or low values in selected assays. NIH describes interference in selected TSH and NT-proBNP assays, and FDA describes the risk of falsely low results in susceptible troponin assays. S08 provides historical safety context for assay interference, not hair efficacy data.", "condition_status": "Partly verified", "status_reason": "Assay-specific warnings and directions were retained, but current official documents and each original study/assay version were not newly compared this time.", "missingness": "Details of assays, versions, specimens, directions of interference, actual exposure and original studies have not been obtained.", "uncertainty": "This does not mean interference in all assays, causation of clinical events or AGA efficacy, and no personal dosing/testing instructions were created.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Assay/version, specimen, direction of interference and actual exposure records in official documents; the corresponding scope if the S08 original is provided." }, { "item_id": "N33", "question_type": "Exposure and time", "question": "Are a single 10 mg dose and 24 hours distinguished from 10 mg/day and 1 week?", "needed": "Exposure start/end, blood draw/testing time points, assay-specific recovery data and the corresponding original official statements.", "role": "Supplementary; required for time interpretation", "role_reason": "Needed to avoid converting different exposures and time points into a universal discontinuation interval or toxicity threshold.", "application_exception": "Observation within 24 hours does not mean a safe discontinuation interval for all people and all assays. Do not estimate re-exposure/recovery values when they are absent.", "criterion": "Attribute single and repeated exposures, the 6 healthy adults and the scope of each assay observation accurately.", "basis": "M19 §19.1.2–19.2.4; in-house application; design-specific harm questions in M19 §19.2; details of temporal relationships are designed in-house — an in-house adaptation of exposure and time; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "Compare exposure–testing timelines by source, distinguishing verified temporal relationships from unverified recovery/discontinuation intervals.", "current_reports": [ "S06", "S08" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The original retained statement about NIH distinguishes thyroid-test interference after a single 10 mg dose, observed within 24 hours, from selected TSH/NT-proBNP interference in 6 healthy adults exposed to 10 mg/day for 1 week. The two exposures and time points are not a universal discontinuation interval or toxicity threshold.", "condition_status": "Partly verified", "status_reason": "Reported exposures and times were linked, but assay-specific details of recovery, discontinuation and re-exposure were not verified this time.", "missingness": "Assay-specific blood draw/recovery, discontinuation and re-exposure times and actual exposure data have not been obtained.", "uncertainty": "Observation within 24 hours was not converted into a safe discontinuation interval for all people/assays.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Exposure start/end, blood draw/testing time points, assay-specific recovery data and the corresponding original official statements." }, { "item_id": "N34", "question_type": "Risk and denominators", "question": "Can interference event counts, denominators and comparative risks be linked?", "needed": "Counts of affected people/assays/events, exposure denominators, testing systems, periods, comparisons and repeat citation links.", "role": "Supplementary; required for extensions to risk/causation", "role_reason": "Needed to avoid converting 6 healthy people or official warnings into estimates of interference incidence or clinical event risk.", "application_exception": "The original source does not provide total event counts, detection denominators or risk comparisons by period. Do not convert the person count of 6 into an event count or frequency.", "criterion": "Link the reported counts of interference events/people/assays with exposure denominators, periods and comparisons, leaving absent risk values Unverified. For official warnings and repeat citations, distinguish signals from risk estimates.", "basis": "M19 §19.1.2–19.2.4; in-house application; M19 §19.2.2–19.2.4, M03 §3.2.3; in-house application; M19 §19.1.2–19.2.4, M04 §4.6.3; in-house application; M04 §4.6.1–4.6.2; adaptation of harm data is designed in-house; Chamgap's own interpretation boundary. Reference to M19 principles, not execution of an official causality tool — an in-house adaptation of risk and denominators; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "When reviewing safety data in the future, group original studies with their official repeat citations and distinguish assay signals, clinical outcomes and comparative risks separately.", "current_reports": [ "S06", "S07", "S08" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The manuscript's assay-interference warning does not provide counts of events/people/assays, incidence by period or comparative risks. The 6 healthy adults are not the total interference event count or a risk denominator. The FDA citation also explicitly states that there is no frequency estimate. Official repeat citations are not added up as independent events.", "condition_status": "Unverified", "status_reason": "Risk values linked to the full collection system, event counts, comparisons, denominators and periods were not verified within the currently retained scope.", "missingness": "Counts of interference events/people/assays, exposure denominators, detection systems, periods, comparisons and the lineage of repeat citations of original studies have not been obtained.", "uncertainty": "Current signals/warnings were not elevated to incidence, comparative risk, causation of clinical events or safety certification.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Counts of affected people/assays/events, exposure denominators, testing systems, periods, comparisons and repeat citation links." }, { "item_id": "N35", "question_type": "Long-term use and vulnerable groups", "question": "Are unverified long-term/vulnerable-group safety and the absence of an established upper intake level distinguished?", "needed": "Data on duration, special populations, actual exposure, harm collection and assay interference, and the evidentiary scope for the UL.", "role": "Supplementary; required for broad safety claims", "role_reason": "Needed to avoid converting short-term assay data in healthy people or the absence of an established UL into a guarantee of safety for long-term hair-loss use.", "application_exception": "The narrow density efficacy question does not require all rare-harm studies as prerequisites for verification. Unlimited safety or personal doses are not presented.", "criterion": "Preserve the unverified status of pregnancy, lactation, children, hepatic/renal disease and long-term high-dose use, and limit the meaning of no-UL.", "basis": "M19 §19.1.2–19.2.4; in-house application; Chamgap's own interpretation boundary. Reference to M19 principles, not execution of an official causality tool — an in-house adaptation of long-term use and vulnerable groups; not official methodological certification.", "condition_origin": "An individually designed development condition informed by the preserved content. Neither blinded validation nor preregistration.", "proposed_research": "When a follow-up safety question is actually requested, review appropriate follow-up/observational designs by exposure and population, and state the retained safety boundaries.", "current_reports": [ "S06", "S07", "S08" ], "existence": "Verification of the locations, values, and identities in the currently preserved archived summaries; separate from whether external documents are currently public or have been acquired.", "acquired_read": "Summary reading: actual reading of the preserved archived summaries. External original papers, registrations, and official web texts were not read in this review.", "observation": "The manuscript retains that safety for hair-loss use with long-term high doses and in pregnancy, lactation, children and hepatic/renal disease is Unverified. NIH's absence of an established upper intake level does not mean unlimited safety or a treatment dose. Short-term assay-interference data in healthy people do not establish broad safety.", "condition_status": "Unverified", "status_reason": "Direct safety data for the relevant exposure durations and vulnerable groups were not verified within the currently retained scope.", "missingness": "Actual exposure, harms/discontinuation, assay interference and follow-up for long-term use/special populations, and the evidentiary scope for the UL, have not been obtained.", "uncertainty": "The narrow efficacy question does not require all rare-harm studies, and no new safe dose or personal instructions were created.", "review_date": "2026-10-05", "reading_status": "Original text: Not read · Archived summary: read", "additional_material": "Data on duration, special populations, actual exposure, harm collection and assay interference, and the evidentiary scope for the UL." } ], "reports": [ { "report_id": "S01", "title": "A Review of the Use of Biotin for Hair Loss (Patel, Swink, Castelo-Soccio, 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "report_type": "narrative_review", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "R-S01", "independent_replication": "The review and its included cases are not added up as independent AGA trials.", "observed_result": "This is a 2017 review, not an RCT. The old synthesis of case reports is retained as discovery context, and is not used as a current exhaustive conclusion of absence or as an AGA non-vellus result for monotherapy.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic/index page", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: provided_extract. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: citations[0], evidence review entry; bibliography cross-reference in S05 p19 refs4", "material_id": "S01-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/28879195/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/28879195/" } ] }, { "report_id": "S02", "title": "Biotin for Hair Loss: Teasing Out the Evidence (Yelich et al., 2024)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11324195/", "report_type": "review", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "R-S02", "independent_replication": "Repeated citation in a review does not mean an independent trial. Original-text details and links to included studies are unresolved.", "observed_result": "It reports the PMC access challenge and publisher/repository failures at that time. Historical trial details were not newly verified, and no DOI was invented and inserted. Only the retained extraction/index wording was read this time.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PMC article full text on the web", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: provided_extract_and_indexed_metadata. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: corresponding citation/evidence; original retrieval failed", "material_id": "S02-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11324195/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11324195/" } ] }, { "report_id": "S03", "title": "Efficacy of 5% topical minoxidil versus 5 mg oral biotin versus topical minoxidil and oral biotin on hair growth in men (Valentim et al., 2024)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11221127/", "report_type": "clinical_study", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F01", "independent_replication": "This is the original evidence label F01. Crossover regimen periods are not counted as independent participants/trials.", "observed_result": "This is a crossover trial in 10 healthy men with 14 days per regimen. It retains growth speed during the biotin 5 mg/day period of 2.50(SD 0.38)→2.47(SD 0.42) mm/week, within-group P=0.53, and within-group P=0.02 during the minoxidil+biotin period. These are not repurposed as AGA non-vellus density, a placebo-adjusted between-group effect or synergy.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PMC article full text on the web", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: full_text. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: Methods paragraphs; Table1 and footnotes; Financial support / Conflicts of interest", "material_id": "S03-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11221127/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11221127/" } ] }, { "report_id": "S04", "title": "Ablon 2015 marine-protein supplement study in women with self-perceived thinning hair", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4389977/", "report_type": "clinical_study_inherited_extract", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F02", "independent_replication": "This is the original evidence label F02 and is not counted as an eligible monotherapy AGA replication trial.", "observed_result": "It was excluded from the direct monotherapy AGA question because it involved a multicomponent marine-protein product and self-reported hair thinning in women. Only the existing extraction was reused, and old numerical effects were not imported into the current manuscript. The PMC challenge at that time is a historical record and is separate from no access attempt this time.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PMC article full text on the web", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: provided_extract. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: corresponding evidence/citation; PMC challenge on current access", "material_id": "S04-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4389977/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4389977/" } ] }, { "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": "clinical_study", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F03", "independent_replication": "Group the article in F03 with the S11 registration. The registration document is not a separate replication trial.", "observed_result": "In healthy participants with nonpathological cosmetic concerns, it reports 105 assigned, 97 completed and 90 days in a trial with 3 arms. Even the biotin-labelled arm used Sesbania extract, with 250 mg extract and 1.25 mg biotin equivalent per capsule. Positive findings and manufacturer/CRO employment relationships are retained, but are not used as direct AGA non-vellus results for monotherapy. The S11 registration belongs to the same lineage, and its history has not been obtained.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher's full-text article PDF", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: full-text document PDF. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: pp1–4 (abstract, Methods, Table2, inclusion); p19 Disclosures", "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=", "parent_url": null } ], "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": "official_safety_document", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "OFF-S06", "independent_replication": "Official documents' repeat citations of original studies are not added up as new independent events/trials.", "observed_result": "The original citation reports the official page's update date of 2022-01-10 and verification of the safety text at that time. The manuscript retains selected assay interference after a single 10 mg dose, within 24 hours, and in 6 healthy adults exposed to 10 mg/day for 1 week. It does not claim that the cited original studies were newly verified in full text at that time, and no-UL does not mean unlimited safety/a treatment dose.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "NIH ODS official web document", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: official_full_text. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: Table1; Health Risks from Excessive Biotin; Interactions with Laboratory Tests, refs9/38", "material_id": "S06-M1", "url": "https://ods.od.nih.gov/factsheets/Biotin-HealthProfessional/", "parent_url": null } ], "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": "official_safety_document", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "OFF-S07", "independent_replication": "Official warnings are not counted as incidence, numbers of independent cases or new causal judgements.", "observed_result": "The original citation reports that the official safety statement on the risk of falsely low results in selected troponin assays was checked at that time. This is not a warning applicable to all assays or a frequency estimate. The external material is currently Not read.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "FDA official web document", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: official_full_text. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: Opening safety statement and paragraphs on residual assay interference", "material_id": "S07-M1", "url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.fda.gov/medical-devices/in-vitro-diagnostics/biotin-interference-troponin-lab-tests-assays-subject-biotin-interference" } ] }, { "report_id": "S08", "title": "Assessment of biotin interference in thyroid function tests (Zhang et al., 2020)", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7478465/", "report_type": "clinical_safety_study_inherited_extract", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F04", "independent_replication": "This is the original F04 safety-study label and is not added to efficacy replications or to events cited again in official sources.", "observed_result": "The original evidence retains only the safety context of assay interference and states that it is not direct evidence of hair efficacy. It reports the PMC challenge/empty PubMed output at that time and reuse of historical extracts, and does not state that a universal washout/discontinuation recommendation was newly verified.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PMC article full text on the web", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: provided_extract. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: corresponding evidence/citation", "material_id": "S08-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7478465/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7478465/" } ] }, { "report_id": "S09", "title": "2026 Dermato systematic-review lead in existing 009", "url": "https://www.mdpi.com/2673-6179/6/2/17", "report_type": "systematic_review_lead_unverified", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "R-S09", "independent_replication": "The review lead is not added to the count of independent trials, and overlap among included studies is unresolved.", "observed_result": "From existing 009, this is the 2026 Dermato review lead. Author details and the full list of included studies were not newly verified at that time, and publisher 429 is recorded. It is not used as an independent trial or as a basis for efficacy grading.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Publisher's review full text on the web", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: indexed_metadata_and_provided_extract. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: corresponding citation; publisher 429", "material_id": "S09-M1", "url": "https://www.mdpi.com/2673-6179/6/2/17", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.mdpi.com/2673-6179/6/2/17" } ] }, { "report_id": "S10", "title": "ClinicalTrials.gov NCT06605768—hair supplement study lead", "url": "https://clinicaltrials.gov/study/NCT06605768", "report_type": "trial_registration_shell", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F05", "independent_replication": "This is the original F05 candidate identity and is not counted as a trial with a verified directly eligible result/independent replication.", "observed_result": "An indexed title/registration pointer exists, but access to the official current protocol/results was incomplete at that time. The product's sole-active-ingredient status, AGA population and non-vellus endpoint are Unverified, and commercial summaries were not adopted as official facts. This is not evidence of no results, negative results or trial termination.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official trial-registration web page", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: registration_shell. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: Study page shell; API unavailable", "material_id": "S10-M1", "url": "https://clinicaltrials.gov/study/NCT06605768", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT06605768" } ] }, { "report_id": "S11", "title": "ClinicalTrials.gov NCT05972512—registration cited by Patel 2025", "url": "https://clinicaltrials.gov/study/NCT05972512", "report_type": "trial_registration_shell", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "F03", "independent_replication": "Preserve the link with S05 in the same F03, without turning the article+registration into two replication trials.", "observed_result": "S05 reports NCT05972512, and the link to it places this registration in the same family. Registration content/history has not been obtained, so comparison of prospective endpoint hierarchy, analyses and time points is Unverified. It is not counted as separate replication.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Official trial-registration web page", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: registration_shell. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: Study page shell; article S05 Methods/Disclosures reports this identifier", "material_id": "S11-M1", "url": "https://clinicaltrials.gov/study/NCT05972512", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT05972512" } ] }, { "report_id": "S12", "title": "The Infatuation With Biotin Supplementation: Is There Truth Behind Its Rising Popularity? (Soleymani et al., 2017)", "url": "https://pubmed.ncbi.nlm.nih.gov/28628687/", "report_type": "narrative_review", "existence": "This is a reference from retained bibliography and historical records; the current external response was not checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the retained manuscript were read. The linked external original materials are Not read this time.", "study_family": "R-S12", "independent_replication": "The review and re-cited cases are not added up as independent direct trials.", "observed_result": "This is a narrative review, not an RCT. The review entry in existing 009 is reused, with no claim of new access to the original at that time. It is not used as a monotherapy AGA non-vellus result or as a current exhaustive-search conclusion of absence.", "result_level": "This is content recorded in the retained manuscript. It is not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "PubMed bibliographic/index page", "public_status": "Unverified (no lookup this time)", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Not read", "as_of": "2026-10-05", "qualification": "No attempt was made to access this external original material or read its original text this time. What was read now was the retained report-specific summary. The bibliographic address is a route to the original source, and does not mean that current external content/bytes were verified. Historical access level in the bibliography: provided_extract. Each material's actual historical access date is Unverified. The retained manuscript's review date of 2026-09-15 is not the access date of the original material. Historical record location: historical reference record 009.json: corresponding review entry", "material_id": "S12-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/28628687/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/28628687/" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations of the intervention.", "review_level": "Reuse of the existing retained HTML and principles from 1585; not a new full-text reading of the methods or official tool execution/certification this time." }, { "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 studies from reports and link them, without omitting a study solely because results are unreported.", "review_level": "Reuse of the existing retained HTML and principles from 1585; not a new full-text reading of the methods or official tool execution/certification this time." }, { "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, missingness, measurement and selective reporting.", "review_level": "Reuse of the existing retained HTML and principles from 1585; not a new full-text reading of the methods or official tool execution/certification this time." }, { "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 the existing retained HTML and principles from 1585; not a new full-text reading of the methods or official tool execution/certification this time." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations and follow-up that differ from efficacy questions. Case reports do not establish incidence.", "review_level": "Reuse of the existing retained HTML and principles from 1585; not a new full-text reading of the methods or official tool execution/certification this time." } ], "status_dictionary": { "Met": "The retained identity, values and interpretation boundaries of this row were verified. This is not sufficiency of efficacy/safety evidence or clinical certification.", "Partly verified": "Some data have been linked, but specific original materials, scope and comparisons remain to be addressed.", "Unverified": "Necessary data/values within the retained scope currently read are Unverified. This does not mean no effect, 0 events or Review incomplete for table preparation.", "Conflicting information": "An original inconsistency within the same item. No arbitrary correction or substitution of a different denominator.", "Not applicable": "The obligation to extend beyond the original narrow question is not applied. This is not a substitute for Not read or Unverified materials.", "Not applicable (spaced label)": "Display alias for Not applicable.", "Not read": "External materials were not directly read this time; this is separate from actually reading the retained archived report summaries.", "Review incomplete": "Individual review for preparing the table remains unfinished. Distinct from insufficient data." }, "study_overlap": { "state": "These are the family labels and report links in the original data. The five labels do not mean five independent direct clinical trials. F01 (S03): original evidence label: a crossover trial of growth speed in healthy people; not directly eligible. / F02 (S04): original evidence label: existing extraction of a multicomponent marine-protein product/self-reported thinning; not directly eligible. / F03 (S05, S11): the original S05 article and registration S11 are linked as the same study. These are adjacent combination/botanical-extract data, with registration history Unverified. / F04 (S08): original evidence label: historical safety context for assay interference; not an efficacy family. / F05 (S10): original evidence label: a registration lead with eligibility/results Unverified. Reviews, official documents and discovery leads: S01, S02, S06, S07, S09, S12. The original family labels and verified S05/S11 link are retained. The detailed family table is Not read, and no totals of independent trials or participants are generated. S05 and S11 are grouped into the same F03, and the registration is not added as a separate replication trial. 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 data. The five labels do not mean five independent direct clinical trials. F01 (S03): original evidence label: a crossover trial of growth speed in healthy people; not directly eligible. / F02 (S04): original evidence label: existing extraction of a multicomponent marine-protein product/self-reported thinning; not directly eligible. / F03 (S05, S11): the original S05 article and registration S11 are linked as the same study. These are adjacent combination/botanical-extract data, with registration history Unverified. / F04 (S08): original evidence label: historical safety context for assay interference; not an efficacy family. / F05 (S10): original evidence label: a registration lead with eligibility/results Unverified. Reviews, official documents and discovery leads: S01, S02, S06, S07, S09, S12. The original family labels and verified S05/S11 link are retained. The detailed family table is Not read, and no totals of independent trials or participants are generated. S05 and S11 are grouped into the same F03, and the registration is not added as a separate replication trial. The number of unique trials, total participants and independent direct replications are Unverified." }, "history": [ { "date": "2026-11-02", "kind": "Separation of public display and data", "view_version": "1.0", "change": "Public-facing display and data were prepared from the existing 35 items. No new clinical search, change in verification status or grading was performed." } ], "language": "en", "translation_date": "2026-11-02" }