{ "title": "Biotin (vitamin B7), sole-active oral product × Increased target-area non-vellus hair density in adult androgenetic alopecia, with separate sex strata", "criteria_version": "NGM-v3103-BIOTIN-AGA-SEX-NONVELLUS-1.0", "criteria_date": "2026-10-05", "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility criteria and reasons for changes, and distinguish variations of the intervention.", "review_level": "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." }, "schema_version": "chamgap-public-criteria-1.0", "condition_origin": "Chamgap’s own application conditions", "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." } ], "language": "en", "translation_date": "2026-11-02" }