{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3016-s1", "verdict_number": "3016", "title": "Medical-grade manuka honey × MGD dry-eye signs: formulation-specific staining and meibomian signals", "view_version": "1.0", "view_created_date": "2026-10-21", "criteria_version": "1.0", "criteria_date": "2026-10-06", "review_date": null, "legacy_evidence_date": "2026-09-07", "review_scope": { "materials_read": "Existing review summaries and stored records of methodological application", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "Existing stored summary and preserved methodology application records. External papers, abstracts, registration, protocols, SAPs, original result tables and support disclosures are unread, and review of existing content remains incomplete.", "date_meaning": "This is the date the stored materials were checked, not the date of a new search of the clinical literature." }, "claim_context": { "population": "Evaporative dry eye from meibomian gland dysfunction. Detailed diagnosis, severity, baseline status, eligibility and group composition remain unverified.", "intervention": "Medical-grade 16% manuka-honey drops or 98% gel were added to existing lid care. Formulations are distinguished from each other and from food-grade or nonsterile products.", "dose": "16% and 98% are concentrations of different formulations. Actual instilled amount, frequency, adherence and exposure remain unverified; concentration is not converted into administered dose.", "comparator": "Common warm compresses, lid massage and preservative-free lubricant in the 2017 trial are distinguished from comparison with regular lubricant in the 2021 trial. Details of matched group care and changes remain unverified.", "endpoint": "Staining with 16% drops P=.035 and meibum quality P=.005 and gland expressibility P=.042 with 98% gel are distinguished by formulation and sign. Supporting-trial within-group SPEED results are not sign estimates.", "duration": "The principal direct trial over 8 weeks is distinguished from the supporting trial over 3 weeks. Sign signals are not converted into permanent gland recovery or long-term effects; post-stopping durability and long-term harms remain unverified.", "excluded_extensions": [ "Selected-signs C and absent individual score are distinguished from parent C46, symptom C and food-honey self-instillation F. Parent score or axes are not newly inherited.", "16% drops and 98% gel are not combined, and medical-grade sterile products are not expanded into evidence for food-grade, nonsterile or homemade-dilution instillation.", "Staining P=.035, meibum quality P=.005 and gland expressibility P=.042 are selected signals linked to their respective formulations and signs. They are not combined into one formulation, scale or overall effect.", "SPEED 2.53 points P=.006 and 1.087 points P=.183 are within-group symptom records from the supporting trial. They are not converted into sign estimates, direct between-group symptom effects, new differences or CIs.", "114 participants and 59 randomized with 55 completed are distinguished without calculating new attrition counts, group, eye, patient or safety denominators, or incidence.", "Shared reports are not counted as new independent replication for each question. Short-term symptoms and signs are not expanded into long-term recovery, treatment replacement or overall safety." ] }, "requirements": [ { "item_id": "N01", "question_type": "Evidence condition", "question": "Which signs question does this evidence check cover?", "needed": "Formulation-specific comparisons for improvement in selected staining and meibomian signs", "role": "Required", "role_reason": "Material on Formulation-specific comparisons for improvement in selected staining and meibomian signs is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Formulation-specific comparisons for improvement in selected staining and meibomian signs must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Selected findings are not expanded into all signs or symptom effects. Original formulation, sign, control and time-specific tables, denominators and CIs require additional material. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The existing selected question is improvement in selected staining or meibomian signs. The original account of formulation-specific signals from a small open multiple-outcome trial is retained.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Selected findings are not expanded into all signs or symptom effects. Original formulation, sign, control and time-specific tables, denominators and CIs require additional material.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Selected findings are not expanded into all signs or symptom effects. Original formulation, sign, control and time-specific tables, denominators and CIs require additional material." }, { "item_id": "N02", "question_type": "Evidence condition", "question": "What does the staining signal with 16% drops represent?", "needed": "Staining measurement with drops, between-group estimates, P values and CIs", "role": "Required", "role_reason": "Material on Staining measurement with drops, between-group estimates, P values and CIs is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Staining measurement with drops, between-group estimates, P values and CIs must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Original staining sites, scales, assessors, time points, groups, denominators, effects and CIs remain unverified. The value is not converted into a symptom or gel result. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The principal trial records staining with drops P=.035 as a selected between-group signal. Exact staining effects, scales and CIs are absent from the stored summary.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Original staining sites, scales, assessors, time points, groups, denominators, effects and CIs remain unverified. The value is not converted into a symptom or gel result.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original staining sites, scales, assessors, time points, groups, denominators, effects and CIs remain unverified. The value is not converted into a symptom or gel result." }, { "item_id": "N03", "question_type": "Evidence condition", "question": "What is the meibum quality signal with 98% gel?", "needed": "The definition, assessment, between-group effect, P values and CIs for gel meibum quality", "role": "Required", "role_reason": "Material on The definition, assessment, between-group effect, P values and CIs for gel meibum quality is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on The definition, assessment, between-group effect, P values and CIs for gel meibum quality must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: The same value is not copied to staining, gland expressibility or all signs. Grades, scales, assessment, expression methods, groups, denominators, time points, effects and CIs remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original principal trial records gel meibum quality P=.005.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "The same value is not copied to staining, gland expressibility or all signs. Grades, scales, assessment, expression methods, groups, denominators, time points, effects and CIs remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "The same value is not copied to staining, gland expressibility or all signs. Grades, scales, assessment, expression methods, groups, denominators, time points, effects and CIs remain unverified." }, { "item_id": "N04", "question_type": "Evidence condition", "question": "What is the gland expressibility signal with 98% gel?", "needed": "Gland expressibility scales, measurement, between-group effects, P values and CIs", "role": "Required", "role_reason": "Material on Gland expressibility scales, measurement, between-group effects, P values and CIs is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Gland expressibility scales, measurement, between-group effects, P values and CIs must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Gland selection, measurement, grades, assessors, groups, time points, denominators, effects and CIs remain unverified. New differences are not calculated. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original principal trial records gel gland expressibility P=.042. It is retained as a separate sign from meibum quality.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Gland selection, measurement, grades, assessors, groups, time points, denominators, effects and CIs remain unverified. New differences are not calculated.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Gland selection, measurement, grades, assessors, groups, time points, denominators, effects and CIs remain unverified. New differences are not calculated." }, { "item_id": "N05", "question_type": "Evidence condition", "question": "How do P values differ from effect size and precision?", "needed": "Sign-specific between-group estimates, variance and 95% CIs", "role": "Required", "role_reason": "Material on Sign-specific between-group estimates, variance and 95% CIs is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Sign-specific between-group estimates, variance and 95% CIs must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: P values alone do not newly verify large effects, precision, cure or equivalence. Original formulation-specific estimates, baseline and changes, denominators, variance, CIs and models remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The stored summary provides selected P values but does not retain exact formulation-specific effect sizes and intervals.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "P values alone do not newly verify large effects, precision, cure or equivalence. Original formulation-specific estimates, baseline and changes, denominators, variance, CIs and models remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "P values alone do not newly verify large effects, precision, cure or equivalence. Original formulation-specific estimates, baseline and changes, denominators, variance, CIs and models remain unverified." }, { "item_id": "N06", "question_type": "Evidence condition", "question": "Are improvement in all groups and added sign effects distinguished?", "needed": "Direct comparison conditions for each formulation and sign versus common care", "role": "Required", "role_reason": "Material on Direct comparison conditions for each formulation and sign versus common care is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Direct comparison conditions for each formulation and sign versus common care must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Overall recovery is not assigned to honey as an ingredient. Common care, formulation-specific baselines, time points, all results and between-group contrast tables remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "Improvement in all groups is the common-care context. Selected between-group sign signals and before-and-after improvement within each group are retained separately.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Overall recovery is not assigned to honey as an ingredient. Common care, formulation-specific baselines, time points, all results and between-group contrast tables remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Overall recovery is not assigned to honey as an ingredient. Common care, formulation-specific baselines, time points, all results and between-group contrast tables remain unverified." }, { "item_id": "N07", "question_type": "Evidence condition", "question": "Can drops, gel, staining and gland measures be interchanged?", "needed": "Matching 16% drop staining to 98% gel quality and expressibility", "role": "Required", "role_reason": "Material on Matching 16% drop staining to 98% gel quality and expressibility is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Matching 16% drop staining to 98% gel quality and expressibility must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: They are not pooled into a combined effect for one product or scale. Formulations, administration, scales, time points, group denominators and direct superiority comparisons remain unverified; formulation equivalence or superiority is not established. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original account distinguishes staining with drops from meibomian measures with gel. The 3 P values link to different formulations and measures.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "They are not pooled into a combined effect for one product or scale. Formulations, administration, scales, time points, group denominators and direct superiority comparisons remain unverified; formulation equivalence or superiority is not established.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "They are not pooled into a combined effect for one product or scale. Formulations, administration, scales, time points, group denominators and direct superiority comparisons remain unverified; formulation equivalence or superiority is not established." }, { "item_id": "N08", "question_type": "Evidence condition", "question": "Are assessors and reproducibility of staining and meibum measurement verified?", "needed": "Original measurement, expression, assessment sites, scales and masking methods", "role": "Required", "role_reason": "Material on Original measurement, expression, assessment sites, scales and masking methods is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Original measurement, expression, assessment sites, scales and masking methods must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Successful assessor masking is not newly added to an open trial. Tests, scales, sites, gland selection, assessors, photographs, video, measurement records and time points remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original outcome list includes staining and meibum, but methods, scales, assessors and agreement are not detailed.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Successful assessor masking is not newly added to an open trial. Tests, scales, sites, gland selection, assessors, photographs, video, measurement records and time points remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Successful assessor masking is not newly added to an open trial. Tests, scales, sites, gland selection, assessors, photographs, video, measurement records and time points remain unverified." }, { "item_id": "N09", "question_type": "Evidence condition", "question": "How do the open 3-group design, multiple outcomes and selected signals relate?", "needed": "Prespecified primary outcomes, multiple signs and time points, and multiplicity plans", "role": "Required", "role_reason": "Material on Prespecified primary outcomes, multiple signs and time points, and multiplicity plans is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Prespecified primary outcomes, multiple signs and time points, and multiplicity plans must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Selected positive P values do not establish prespecified primary-outcome success or positive findings for all outcomes. Registration, protocols, analysis plans, all result tables and multiplicity remain unverified; no new official risk assessment is created. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original selected explanation and principal report retain the limitation of a small open multiple-outcome trial.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Selected positive P values do not establish prespecified primary-outcome success or positive findings for all outcomes. Registration, protocols, analysis plans, all result tables and multiplicity remain unverified; no new official risk assessment is created.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Selected positive P values do not establish prespecified primary-outcome success or positive findings for all outcomes. Registration, protocols, analysis plans, all result tables and multiplicity remain unverified; no new official risk assessment is created." }, { "item_id": "N10", "question_type": "Evidence condition", "question": "Does the supporting trial's signs list also provide exact effects?", "needed": "Tear-film, inflammation and staining results from the 59-participant trial", "role": "Required", "role_reason": "Material on Tear-film, inflammation and staining results from the 59-participant trial is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Tear-film, inflammation and staining results from the 59-participant trial must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: SPEED values or P values are not copied into sign results. Original sign-specific results, time points, denominators, formulation, hierarchy, between-group effects and CIs remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The supporting trial's outcomes are 3-week SPEED, tear film, inflammation and staining. The stored result values are within-group SPEED changes.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "SPEED values or P values are not copied into sign results. Original sign-specific results, time points, denominators, formulation, hierarchy, between-group effects and CIs remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "SPEED values or P values are not copied into sign results. Original sign-specific results, time points, denominators, formulation, hierarchy, between-group effects and CIs remain unverified." }, { "item_id": "N11", "question_type": "Evidence condition", "question": "Are symptom superiority and sign signals different questions?", "needed": "The boundary of direct results for selected signs and the symptom question", "role": "Supplementary", "role_reason": "Material on The boundary of direct results for selected signs and the symptom question is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on The boundary of direct results for selected signs and the symptom question must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Original symptom and sign tables, denominators, scales and matching within the same cohort remain unverified. Shared reports across the questions are not counted as separate independent replication. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The parent and symptom question retain a gap in direct between-group symptom effects. Selected sign signals do not become symptom verification or new independent trials.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Original symptom and sign tables, denominators, scales and matching within the same cohort remain unverified. Shared reports across the questions are not counted as separate independent replication.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original symptom and sign tables, denominators, scales and matching within the same cohort remain unverified. Shared reports across the questions are not counted as separate independent replication." }, { "item_id": "N12", "question_type": "Evidence condition", "question": "Do tear film, colonization and lubricant use share the same effect?", "needed": "Separate outcomes for other ocular-surface measures, mechanisms and medication use", "role": "Supplementary", "role_reason": "Material on Separate outcomes for other ocular-surface measures, mechanisms and medication use is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Separate outcomes for other ocular-surface measures, mechanisms and medication use must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: The selected 3 P values are not used as effects on remaining outcomes, clinical symptoms or infection prevention. Each original outcome, hierarchy, value, denominator and between-group contrast remains unverified; unrecorded effects or CIs are not created. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The principal trial's outcome list also includes tear film, colonization and lubricant use.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "The selected 3 P values are not used as effects on remaining outcomes, clinical symptoms or infection prevention. Each original outcome, hierarchy, value, denominator and between-group contrast remains unverified; unrecorded effects or CIs are not created.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "The selected 3 P values are not used as effects on remaining outcomes, clinical symptoms or infection prevention. Each original outcome, hierarchy, value, denominator and between-group contrast remains unverified; unrecorded effects or CIs are not created." }, { "item_id": "N13", "question_type": "Evidence condition", "question": "How are the principal 8 weeks, supporting 3 weeks and long-term recovery distinguished?", "needed": "Sign-specific time points, exposure, post-stopping and long-term follow-up", "role": "Supplementary", "role_reason": "Material on Sign-specific time points, exposure, post-stopping and long-term follow-up is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Sign-specific time points, exposure, post-stopping and long-term follow-up must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Sign signals are not expanded into permanent gland recovery or long-term durability. Report-specific sign time points, administration, long-term and post-stopping course and direct results remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original principal direct trial spans 8 weeks and the supporting trial 3 weeks. Durations from different reports are distinguished.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Sign signals are not expanded into permanent gland recovery or long-term durability. Report-specific sign time points, administration, long-term and post-stopping course and direct results remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Sign signals are not expanded into permanent gland recovery or long-term durability. Report-specific sign time points, administration, long-term and post-stopping course and direct results remain unverified." }, { "item_id": "N14", "question_type": "Evidence condition", "question": "How are medical-grade sterile products distinguished from food honey?", "needed": "Manufacture, quality and actual administration of medical-grade 16% drops and 98% gel", "role": "Required", "role_reason": "Material on Manufacture, quality and actual administration of medical-grade 16% drops and 98% gel is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Manufacture, quality and actual administration of medical-grade 16% drops and 98% gel must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Product, sterility, ingredients, manufacture, dose, frequency and administration records remain unverified in detail. Medical-grade product records are not expanded into effects of food-grade or nonsterile products. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original record concerns ophthalmic medical-grade products, not evidence for food-grade manuka honey or homemade dilution. Concentration differs from actual instilled amount and frequency.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Product, sterility, ingredients, manufacture, dose, frequency and administration records remain unverified in detail. Medical-grade product records are not expanded into effects of food-grade or nonsterile products.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Product, sterility, ingredients, manufacture, dose, frequency and administration records remain unverified in detail. Medical-grade product records are not expanded into effects of food-grade or nonsterile products." }, { "item_id": "N15", "question_type": "Evidence condition", "question": "What was added to common lid care?", "needed": "Warm compresses, massage, preservative-free lubricant and formulation-specific additional care", "role": "Required", "role_reason": "Material on Warm compresses, massage, preservative-free lubricant and formulation-specific additional care is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Warm compresses, massage, preservative-free lubricant and formulation-specific additional care must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: It is not converted into evidence for stopping care or standalone treatment. Common-care rules, adherence, additional and rescue medications, formulation-specific matching and changes remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "In 2017, all groups used common warm compresses, lid massage and preservative-free lubricant. The comparison added medical-grade honey products to that care.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "It is not converted into evidence for stopping care or standalone treatment. Common-care rules, adherence, additional and rescue medications, formulation-specific matching and changes remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "It is not converted into evidence for stopping care or standalone treatment. Common-care rules, adherence, additional and rescue medications, formulation-specific matching and changes remain unverified." }, { "item_id": "N16", "question_type": "Evidence condition", "question": "Are MGD diagnosis and sample size the same information?", "needed": "Diagnosis, severity, baseline status and group-specific eligibility in evaporative dry eye", "role": "Required", "role_reason": "Material on Diagnosis, severity, baseline status and group-specific eligibility in evaporative dry eye is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Diagnosis, severity, baseline status and group-specific eligibility in evaporative dry eye must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Sample size does not replace diagnostic or eligibility criteria. Diagnosis, severity, baseline symptoms and signs, age, comorbidities and group-specific inclusion and exclusion remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The parent question concerns evaporative dry eye from meibomian gland dysfunction. 114 participants is the original sample-size label.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Sample size does not replace diagnostic or eligibility criteria. Diagnosis, severity, baseline symptoms and signs, age, comorbidities and group-specific inclusion and exclusion remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Sample size does not replace diagnostic or eligibility criteria. Diagnosis, severity, baseline symptoms and signs, age, comorbidities and group-specific inclusion and exclusion remain unverified." }, { "item_id": "N17", "question_type": "Evidence condition", "question": "What are the selected-sign denominators in 114 participants and 3 groups?", "needed": "Group allocation, completion, analysis and endpoint-specific eye and patient denominators", "role": "Required", "role_reason": "Material on Group allocation, completion, analysis and endpoint-specific eye and patient denominators is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Group allocation, completion, analysis and endpoint-specific eye and patient denominators must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Group allocation, completion, formulations, care groups, endpoints, time points, bilateral-eye and patient denominators and exclusions remain unverified. Denominators absent from the original are not created. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The principal trial's sample was 114 participants and its design was an open 3-group randomized trial.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Group allocation, completion, formulations, care groups, endpoints, time points, bilateral-eye and patient denominators and exclusions remain unverified. Denominators absent from the original are not created.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Group allocation, completion, formulations, care groups, endpoints, time points, bilateral-eye and patient denominators and exclusions remain unverified. Denominators absent from the original are not created." }, { "item_id": "N18", "question_type": "Evidence condition", "question": "What denominators are 59 randomized and 55 completed?", "needed": "Supporting-trial allocation, completion, analysis and group, eye and patient endpoint denominators", "role": "Required", "role_reason": "Material on Supporting-trial allocation, completion, analysis and group, eye and patient endpoint denominators is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Supporting-trial allocation, completion, analysis and group, eye and patient endpoint denominators must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Attrition counts or group-specific and endpoint-specific analysis denominators are not calculated or established. Group flow, reasons, time points and eye and patient denominators remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The supporting trial originally recorded 59 randomized and 55 completed. These values describe separate stages.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Attrition counts or group-specific and endpoint-specific analysis denominators are not calculated or established. Group flow, reasons, time points and eye and patient denominators remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Attrition counts or group-specific and endpoint-specific analysis denominators are not calculated or established. Group flow, reasons, time points and eye and patient denominators remain unverified." }, { "item_id": "N19", "question_type": "Evidence condition", "question": "What is the impact of missingness, attrition and measurement exclusions?", "needed": "Group flow, missing selected-sign outcomes, analysis populations and sensitivity analyses", "role": "Required", "role_reason": "Material on Group flow, missing selected-sign outcomes, analysis populations and sensitivity analyses is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Group flow, missing selected-sign outcomes, analysis populations and sensitivity analyses must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Unread external material is not converted into absence of missingness. Missingness, stopping, exclusions, ITT and completer analyses, missing-data handling, sensitivity and group and eye matching remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "Overall sample and completion records exist, but endpoint-specific missingness, attrition reasons and analysis conditions are not detailed.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Unread external material is not converted into absence of missingness. Missingness, stopping, exclusions, ITT and completer analyses, missing-data handling, sensitivity and group and eye matching remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Unread external material is not converted into absence of missingness. Missingness, stopping, exclusions, ITT and completer analyses, missing-data handling, sensitivity and group and eye matching remain unverified." }, { "item_id": "N20", "question_type": "Evidence condition", "question": "What were the baseline adjustment, change and testing conditions?", "needed": "The effect of interest, baseline adjustment, change and final values, and variance", "role": "Required", "role_reason": "Material on The effect of interest, baseline adjustment, change and final values, and variance is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on The effect of interest, baseline adjustment, change and final values, and variance must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Original analysis plans, statistical tables, baseline and changes, within-eye and within-person correlation, models and CIs remain unverified. New effects or CIs are not back-calculated. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "Original P values and selected changes are retained, but detailed adjustment, variance, time points, denominators and effects of interest remain unread in external originals.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Original analysis plans, statistical tables, baseline and changes, within-eye and within-person correlation, models and CIs remain unverified. New effects or CIs are not back-calculated.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Original analysis plans, statistical tables, baseline and changes, within-eye and within-person correlation, models and CIs remain unverified. New effects or CIs are not back-calculated." }, { "item_id": "N21", "question_type": "Evidence condition", "question": "Does a registration number also verify prespecified plans?", "needed": "Registration, history, primary outcomes, changes and original plans for both trials", "role": "Required", "role_reason": "Material on Registration, history, primary outcomes, changes and original plans for both trials is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Registration, history, primary outcomes, changes and original plans for both trials must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: The number's existence is not promoted into registration reading in this work, prespecification, hierarchy at all time points or plan adherence. Official registration history, protocols and analysis plans were unread in this work. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "Registration was unverified for the principal trial, while NCT04457648 was recorded for the supporting trial.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "The number's existence is not promoted into registration reading in this work, prespecification, hierarchy at all time points or plan adherence. Official registration history, protocols and analysis plans were unread in this work.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "The number's existence is not promoted into registration reading in this work, prespecification, hierarchy at all time points or plan adherence. Official registration history, protocols and analysis plans were unread in this work." }, { "item_id": "N22", "question_type": "Evidence condition", "question": "Do parent and subquestions share the same reports?", "needed": "Report, trial and participant links between the symptom question and other questions", "role": "Required", "role_reason": "Material on Report, trial and participant links between the symptom question and other questions is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Report, trial and participant links between the symptom question and other questions must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Sheet counts are not counted as new studies or independent replications. Report, trial, registration, sample, institution, timing and additional-report matching and unique trial and participant totals remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The parent and subquestions share the same Albietz 2017 and Wong 2021 reports.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Sheet counts are not counted as new studies or independent replications. Report, trial, registration, sample, institution, timing and additional-report matching and unique trial and participant totals remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Sheet counts are not counted as new studies or independent replications. Report, trial, registration, sample, institution, timing and additional-report matching and unique trial and participant totals remain unverified." }, { "item_id": "N23", "question_type": "Evidence condition", "question": "Is independent replication across teams, products and formulations verified?", "needed": "Unique trials and independent teams for the same selected signs, formulation, population, comparison and time point", "role": "Supplementary", "role_reason": "Material on Unique trials and independent teams for the same selected signs, formulation, population, comparison and time point is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Unique trials and independent teams for the same selected signs, formulation, population, comparison and time point must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Different reports or assessor masking alone do not newly establish independent teams or replication under the same conditions. Team, institution, product, funding, participant, effect and denominator matching remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The bibliographies of both reports retain an Albietz author and the specific Optimel product context.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Different reports or assessor masking alone do not newly establish independent teams or replication under the same conditions. Team, institution, product, funding, participant, effect and denominator matching remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Different reports or assessor masking alone do not newly establish independent teams or replication under the same conditions. Team, institution, product, funding, participant, effect and denominator matching remain unverified." }, { "item_id": "N24", "question_type": "Evidence condition", "question": "How much is known about product provision and company involvement?", "needed": "Trial-specific funding, product support, employee authors and conflicts", "role": "Required", "role_reason": "Material on Trial-specific funding, product support, employee authors and conflicts is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Trial-specific funding, product support, employee authors and conflicts must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Unrecorded funding, employee relationships, analysis and publication roles remain unverified. Product provision is not treated as verification of every involvement route or as absence of independence. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The principal trial records Optimel product provision and related involvement; the supporting trial records a specific Optimel product, provision and author conflict disclosure.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Unrecorded funding, employee relationships, analysis and publication roles remain unverified. Product provision is not treated as verification of every involvement route or as absence of independence.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Unrecorded funding, employee relationships, analysis and publication roles remain unverified. Product provision is not treated as verification of every involvement route or as absence of independence." }, { "item_id": "N25", "question_type": "Evidence condition", "question": "What is the scope of reported stinging and redness?", "needed": "Medical-grade product adverse reactions, collection methods, stopping and controls", "role": "Supplementary", "role_reason": "Material on Medical-grade product adverse reactions, collection methods, stopping and controls is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Medical-grade product adverse reactions, collection methods, stopping and controls must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Event counts, incidence or new causality are not created. Collection methods, group and formulation-specific events, severity, timing, stopping, missingness and controls remain unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original record reports temporary stinging and redness and cautions that initial symptoms are possible even with medical-grade formulations.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Event counts, incidence or new causality are not created. Collection methods, group and formulation-specific events, severity, timing, stopping, missingness and controls remain unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Event counts, incidence or new causality are not created. Collection methods, group and formulation-specific events, severity, timing, stopping, missingness and controls remain unverified." }, { "item_id": "N26", "question_type": "Evidence condition", "question": "What are the eye and patient harm denominators and exposures?", "needed": "Safety populations, eyes, patients, formulations, durations and actual instillation exposure", "role": "Supplementary", "role_reason": "Material on Safety populations, eyes, patients, formulations, durations and actual instillation exposure is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Safety populations, eyes, patients, formulations, durations and actual instillation exposure must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Safety denominators, actual instillation, group, eye and formulation-specific events, stopping, exposure and controls remain unverified. Incidence is not calculated. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "114 participants, 59 randomized and 55 completed do not verify safety denominators. Concentrations, formulations, 3 and 8 weeks and common care are not combined as the same harm exposure.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Safety denominators, actual instillation, group, eye and formulation-specific events, stopping, exposure and controls remain unverified. Incidence is not calculated.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Safety denominators, actual instillation, group, eye and formulation-specific events, stopping, exposure and controls remain unverified. Incidence is not calculated." }, { "item_id": "N27", "question_type": "Evidence condition", "question": "Are food or nonsterile risks distinguished from medical-grade product reactions?", "needed": "Manufacture, sterility, baseline eye conditions, other causes and clinical course", "role": "Supplementary", "role_reason": "Material on Manufacture, sterility, baseline eye conditions, other causes and clinical course is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Manufacture, sterility, baseline eye conditions, other causes and clinical course must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: The food-honey self-instillation question is distinguished and no new case is created. Products, baseline eye conditions, concurrent use, event timing, alternative causes, controls and course remain unverified; no new harm causality is judged. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The original caution distinguishes infection and corneal-injury risks with food-grade, nonsterile and homemade dilutions from initial stinging and redness with medical-grade products.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "The food-honey self-instillation question is distinguished and no new case is created. Products, baseline eye conditions, concurrent use, event timing, alternative causes, controls and course remain unverified; no new harm causality is judged.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "The food-honey self-instillation question is distinguished and no new case is created. Products, baseline eye conditions, concurrent use, event timing, alternative causes, controls and course remain unverified; no new harm causality is judged." }, { "item_id": "N28", "question_type": "Evidence condition", "question": "Are long-term, rare and vulnerable-population harms verified?", "needed": "Long exposure, independent harm reports, vulnerable populations and follow-up", "role": "Supplementary", "role_reason": "Material on Long exposure, independent harm reports, vulnerable populations and follow-up is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on Long exposure, independent harm reports, vulnerable populations and follow-up must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: Long follow-up, independent harm reports, vulnerable populations, exposure, denominators, concurrent use and course remain unverified. No external search or new harm judgment was performed in this work. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "Small short-term trials of specific products and descriptions of temporary reactions do not verify long-term, rare or vulnerable-population safety.", "condition_status": "Unverified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "Long follow-up, independent harm reports, vulnerable populations, exposure, denominators, concurrent use and course remain unverified. No external search or new harm judgment was performed in this work.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "Long follow-up, independent harm reports, vulnerable populations, exposure, denominators, concurrent use and course remain unverified. No external search or new harm judgment was performed in this work." }, { "item_id": "N29", "question_type": "Evidence condition", "question": "How does stored-summary reading differ from reading external originals?", "needed": "The complete stored summary and the reading scope for external abstracts, full texts, registration and plans", "role": "Required", "role_reason": "Material on The complete stored summary and the reading scope for external abstracts, full texts, registration and plans is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on The complete stored summary and the reading scope for external abstracts, full texts, registration and plans must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: URLs, numbers and historical verification wording do not establish current reading, successful access or fulfilled conditions. External detailed-material availability, acquisition and actual reading remain separately unverified. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The complete parent Korean and English summary, reports and citations were read. PubMed URLs and registration numbers are existing records; external abstracts, full texts, registration, protocols and analysis plans were unread in this work.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "URLs, numbers and historical verification wording do not establish current reading, successful access or fulfilled conditions. External detailed-material availability, acquisition and actual reading remain separately unverified.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "URLs, numbers and historical verification wording do not establish current reading, successful access or fulfilled conditions. External detailed-material availability, acquisition and actual reading remain separately unverified." }, { "item_id": "N30", "question_type": "Evidence condition", "question": "What do selected C, parent C46, dates and empty values record?", "needed": "The selected grade, absent individual score, parent axes, evidence date and corrections", "role": "Required", "role_reason": "Material on The selected grade, absent individual score, parent axes, evidence date and corrections is needed to connect the medical-grade product, formulation-specific sign, existing care, population, comparison, measurement, time point, eye and patient denominators, precision and harms.", "application_exception": "Selected-signs C and absent individual score, status and axes are retained, distinguishing parent C46, symptom C and food-honey self-instillation F. Formulations, signs and P values are not combined or converted into symptoms or long-term recovery. Supporting within-group SPEED values are not transferred to signs or between-group symptom effects. No new effects, CIs, differences, attrition counts, incidence, denominators, unique totals, grades or individual-care guidance are created.", "criterion": "Original material on The selected grade, absent individual score, parent axes, evidence date and corrections must link to the same question, control, endpoint, time point and denominators, distinguishing within- and between-group results, parent context and unread external materials.", "basis": "Preserved principles distinguishing questions, direct comparisons, reports and trials, endpoints, denominators, precision and harms informed production.", "condition_origin": "These are formulation-specific evidence conditions for the existing subquestion of improvement in selected staining or meibomian signs. They do not establish preregistration, execution of an official assessment tool or completed clinical content review.", "proposed_research": "Material needed: The parent's 46 points are not assigned as a subclaim score, and the historical evidence date is not changed into a new search, external reading or completed-review date. New material, condition revisions and verdict changes are separate events. This records needed materials; no new research was executed.", "current_reports": [ "R01", "R02" ], "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "Complete stored parent Korean and English summary, selected question and bibliography read; external abstracts, full text, registration, protocols and analysis plans unread", "observation": "The selected grade is C, with no individual score, status or axes fields. Parent C46, caution, axes, Korean and English records, 2026-09-07 and empty correction and deliberation records are preserved separately.", "condition_status": "Partly verified", "status_reason": "This state links partial information and gaps in the preserved selected and parent accounts. External verification and clinical content review remain incomplete; it does not certify fulfilled conditions, efficacy, safety, prespecification or independence.", "missingness": "The parent's 46 points are not assigned as a subclaim score, and the historical evidence date is not changed into a new search, external reading or completed-review date. New material, condition revisions and verdict changes are separate events.", "uncertainty": "Exact formulation-specific sign effects, CIs, scales, measurement and reproducibility, group and eye denominators, baseline adjustment, missingness, prespecified hierarchy, exposure, independence, long-term effects and harms remain unverified. Original P values and historical verification wording are not promoted into new calculations, current external reading or completed clinical review.", "review_date": null, "reading_status": "Full text not read · Stored summary read", "additional_material": "The parent's 46 points are not assigned as a subclaim score, and the historical evidence date is not changed into a new search, external reading or completed-review date. New material, condition revisions and verdict changes are separate events." } ], "reports": [ { "report_id": "R01", "title": "Albietz JM·Lenton LM. 2017", "url": "https://pubmed.ncbi.nlm.nih.gov/28585260/", "report_type": "Open 3-group randomized trial", "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "The complete stored parent Korean and English summary, original reports and citations were read. External abstracts, full texts, registration, protocols and analysis plans were unread in this work.", "study_family": "Parent 3016 and the symptom and selected-sign questions share 2 reports, Albietz 2017 and Wong 2021. Shared authors and the specific Optimel product context are retained, while exact sample overlap, unique trial and participant totals and independent replication remain unverified.", "independent_replication": "Parent 3016 and the symptom and selected-sign questions share 2 reports, Albietz 2017 and Wong 2021. Shared authors and the specific Optimel product context are retained, while exact sample overlap, unique trial and participant totals and independent replication remain unverified.", "observed_result": "The original comparison in 114 participants added 16% drops or 98% gel to common care. All groups improved; selected sign signals included staining with drops P=.035 and gel meibum quality P=.005 and gland expressibility P=.042.", "result_level": "These are selected formulation-specific sign signals from the principal open multiple-outcome trial. The original principal duration is 8 weeks; exact sign effects, CIs, scales, measurement, eye and patient denominators and prespecified hierarchy remain unverified. Symptom superiority, formulation superiority and permanent gland recovery are not established.", "source_evidence_date": "2026-09-07", "materials": [ { "material_type": "Stored existing review summary", "public_status": "Preserved copy of the complete parent-verdict stored summary", "access_status": "Stored summary", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T13:02:14.262787+09:00", "qualification": "PMID28585260, DOI10.1111/cxo.12524 and the original record of Optimel product provision and related involvement are retained. Registration details, product contracts, funding and author roles are unread externally; unverified information is not converted into absence. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "External abstract", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID28585260, DOI10.1111/cxo.12524 and the original record of Optimel product provision and related involvement are retained. Registration details, product contracts, funding and author roles are unread externally; unverified information is not converted into absence. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "External full text", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID28585260, DOI10.1111/cxo.12524 and the original record of Optimel product provision and related involvement are retained. Registration details, product contracts, funding and author roles are unread externally; unverified information is not converted into absence. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "Registration material", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID28585260, DOI10.1111/cxo.12524 and the original record of Optimel product provision and related involvement are retained. Registration details, product contracts, funding and author roles are unread externally; unverified information is not converted into absence. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "Protocol and analysis plan", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID28585260, DOI10.1111/cxo.12524 and the original record of Optimel product provision and related involvement are retained. Registration details, product contracts, funding and author roles are unread externally; unverified information is not converted into absence. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/28585260/" } ] }, { "report_id": "R02", "title": "Wong D et al. 2021", "url": "https://pubmed.ncbi.nlm.nih.gov/33419788/", "report_type": "Assessor-masked randomized trial", "existence": "Displayed selected and parent records exist in the stored summary. External availability, acquisition, content and reading of detailed materials remain separately unverified.", "acquired_read": "The complete stored parent Korean and English summary, original reports and citations were read. External abstracts, full texts, registration, protocols and analysis plans were unread in this work.", "study_family": "Parent 3016 and the symptom and selected-sign questions share 2 reports, Albietz 2017 and Wong 2021. Shared authors and the specific Optimel product context are retained, while exact sample overlap, unique trial and participant totals and independent replication remain unverified.", "independent_replication": "Parent 3016 and the symptom and selected-sign questions share 2 reports, Albietz 2017 and Wong 2021. Shared authors and the specific Optimel product context are retained, while exact sample overlap, unique trial and participant totals and independent replication remain unverified.", "observed_result": "59 randomized and 55 completed were recorded, with 3-week within-group SPEED changes of 2.53 points P=.006 for honey drops and 1.087 points P=.183 for regular lubricant. The stored summary states that the abstract did not present a direct between-group symptom effect.", "result_level": "Tear film, inflammation and staining appear in the supporting trial outcome list, but the original numeric results are within-group SPEED changes. They are not converted into sign effects or direct between-group symptom effects. Assessor masking is not promoted into participant or treatment-provider masking, and new differences, CIs, attrition counts or safety denominators are not calculated.", "source_evidence_date": "2026-09-07", "materials": [ { "material_type": "Stored existing review summary", "public_status": "Preserved copy of the complete parent-verdict stored summary", "access_status": "Stored summary", "acquired": true, "actually_read": "Summary read", "as_of": "2026-10-06T13:02:14.262787+09:00", "qualification": "PMID33419788, DOI10.1136/bjophthalmol-2020-317506, NCT04457648, specific Optimel product provision and author conflict disclosure are retained. The number does not establish registration reading in this work, prespecification or plan adherence; disclosure details are unread. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "External abstract", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID33419788, DOI10.1136/bjophthalmol-2020-317506, NCT04457648, specific Optimel product provision and author conflict disclosure are retained. The number does not establish registration reading in this work, prespecification or plan adherence; disclosure details are unread. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "External full text", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID33419788, DOI10.1136/bjophthalmol-2020-317506, NCT04457648, specific Optimel product provision and author conflict disclosure are retained. The number does not establish registration reading in this work, prespecification or plan adherence; disclosure details are unread. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "Registration material", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID33419788, DOI10.1136/bjophthalmol-2020-317506, NCT04457648, specific Optimel product provision and author conflict disclosure are retained. The number does not establish registration reading in this work, prespecification or plan adherence; disclosure details are unread. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." }, { "material_type": "Protocol and analysis plan", "public_status": "Original bibliographic link or needed material; external public availability/access status unverified", "access_status": "Unread; access not attempted", "acquired": false, "actually_read": "Not read", "as_of": null, "qualification": "PMID33419788, DOI10.1136/bjophthalmol-2020-317506, NCT04457648, specific Optimel product provision and author conflict disclosure are retained. The number does not establish registration reading in this work, prespecification or plan adherence; disclosure details are unread. The stored-summary material date 2026-10-06T13:02:14.262787+09:00 is an original production record; unread external material dates are empty. The historical evidence date 2026-09-07 is distinguished from this publication, external reading or completed clinical review." } ], "links": [ { "label": "PubMed", "url": "https://pubmed.ncbi.nlm.nih.gov/33419788/" } ] } ], "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 conditions and reasons for changes, and distinguish variations in interventions.", "review_level": "Existing methodological links were reused for production. External originals were not reread and methodological content was not reassessed." }, { "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; do not omit a study solely because results are unreported.", "review_level": "Existing methodological links were reused for production. External originals were not reread and methodological content was not reassessed." }, { "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": "Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Existing methodological links were reused for production. External originals were not reread and methodological content was not reassessed." }, { "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": "Existing methodological links were reused for production. External originals were not reread and methodological content was not reassessed." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates.", "review_level": "Existing methodological links were reused for production. External originals were not reread and methodological content was not reassessed." } ], "status_dictionary": { "Partly verified": "Partial information from the stored summary is linked; detailed originals and content review remain incomplete.", "Unverified": "Required details cannot be established within the preserved scope. This does not establish absence of effects or studies, or safety.", "Review incomplete": "Review of existing content remains incomplete.", "Met": "This state is used only within the relevant conditions after material verification and content review. It was not automatically assigned in this work.", "Not reported": "Unreported within material actually read. Unread external material is not relabeled as unreported.", "Inaccessible": "This means actual access failure. External access was not attempted in this work, so this state was not assigned.", "Not applicable": "Used only with an application exception and reason based on the question scope.", "Conflicting data": "This requires actual comparison of materials; no new conflict judgment was made in this work.", "Insufficient evidence for the conditions": "This indicates gaps in additional material for the selected conditions. Unread material as a whole is not converted into an efficacy grade." }, "study_overlap": { "state": "Unverified", "unique_trial_count": null, "unique_participant_count": null, "reason": "Parent 3016 and the symptom and selected-sign questions share 2 reports, Albietz 2017 and Wong 2021. Shared authors and the specific Optimel product context are retained, while exact sample overlap, unique trial and participant totals and independent replication remain unverified." }, "history": [ { "date": "2026-10-21", "kind": "Separation of public-facing pages and materials", "view_version": "1.0", "change": "Public-facing views and materials were prepared from the existing 30 items. No new clinical search, verification-status change or scoring was performed." } ], "language": "en", "translation_date": "2026-10-21" }