{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3093-main", "verdict_number": "3093", "title": "Nicotinamide riboside (NR; salt and product details unverified) × Improvement of usual gait speed in frail older adults", "view_version": "1.0", "view_created_date": "2026-11-01", "criteria_version": "NGM-v3093-NR-FRAIL-USUAL-GAIT-1.0", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Retained Korean and English manuscripts and case-specific conditions and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "External clinical abstracts, full texts, registrations, and analysis plans were not newly read. Historical access records are distinguished from this reading of retained summaries. The original judgments, numerical values, and unverified matters are preserved; no new search, calculation, or reassessment was performed.", "date_meaning": "This is the date the retained materials were reviewed, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Community-dwelling adults aged 75 or older with a Fried Frailty Phenotype score of 3 or higher; baseline gait speed and nutritional status unverified", "intervention": "Nicotinamide riboside (NR; salt and product details unverified)", "dose": "Planned 2000 mg/day; amount per dose, frequency, dose escalation, and basis for salt conversion unverified", "comparator": "Placebo (exact composition, matching method, and common care unverified)", "endpoint": "Between-group difference in change in usual gait speed from baseline to week 52 (m/s); the page's primary endpoint, with its actual trial hierarchy and usual-speed protocol unverified", "duration": "Planned 52 weeks; actual exposure and follow-up after discontinuation unverified", "excluded_extensions": [ "6-minute walk distance and WIQ self-reported speed", "Maximal speed, SPPB, muscle strength, fatigue, and chair rise", "Cognition and NAD biomarkers", "Direct transfer of findings from MCI, healthy participants, PAD, and prefrailty", "NMN, NAM, niacin, NAD/NADH, tryptophan, and combination products", "Optimal dose, persistence after discontinuation, prevention of falls/death, and individual safety" ] }, "requirements": [ { "item_id": "N01", "question_type": "Independent question", "question": "Does the table address only the between-group change in usual gait speed in frail older adults?", "needed": "Explicit boundaries of the original claim, population, planned oral NR, placebo, and change in usual speed at 52 weeks", "role": "Required", "role_reason": "Needed to avoid combining the ingredient's overall functions or different walking endpoints into a single effect.", "application_exception": "If the frailty definition or endpoint actually changes, reassess whether separation is needed while retaining the link to the same original ID. Do not automatically create a new table for another combination.", "criterion": "Link the original /ko/effect to the question identity and identify 6-minute walk distance, muscle strength, cognition, and NAD results as separate questions.", "basis": "Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "In a new study, specify usual speed as a single outcome of interest and prespecify the population, comparison, measurement time points, and analysis.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The original claim is improvement of usual gait speed in frail older adults. The single question addresses community-dwelling adults aged 75 or older with a Fried score of 3 or higher, a planned oral NR regimen of 2,000 mg/day for 52 weeks versus placebo, and change in usual speed (m/s).", "condition_status": "Verified", "status_reason": "The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy.", "missingness": "The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy.", "uncertainty": "The claim boundaries are specified in the identity of the retained assessment question. Verification of these boundaries does not verify a completed trial yielding that result or verify efficacy.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Explicit boundaries of the original claim, population, planned oral NR, placebo, and change in usual speed at 52 weeks" }, { "item_id": "N02", "question_type": "Ingredient identity", "question": "Are the NR salt, product, dosage form, and batch in the plan verified?", "needed": "Documentation of the exact NR salt, product, manufacturer, assayed purity, batch, and release form in NADage", "role": "Required", "role_reason": "Needed to avoid directly transferring results and safety findings from different salts, dosage forms, or products.", "application_exception": "If the original source does not clarify the relationship between salt mass and active-moiety amount, retain the reported mg without conversion.", "criterion": "Verify the identity of the substance actually used in this plan; do not substitute NIAGEN or NR chloride information from another trial.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "A suitable comparative study records the test product's analytical results, batch, and active ingredient together with the placebo composition to define a reproducible exposure.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The ingredient is retained as NR, but its salt, crystal form, brand, manufacturer, manufacturing source, dosage form, purity, batch, and release form are unverified. NIAGEN information from another trial was not copied into this plan.", "condition_status": "Unverified", "status_reason": "The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion.", "missingness": "The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion.", "uncertainty": "The retained identity fields are null or unverified. The molecular name NR alone cannot verify an identical salt, product, or basis for exposure conversion.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Documentation of the exact NR salt, product, manufacturer, assayed purity, batch, and release form in NADage" }, { "item_id": "N03", "question_type": "Single intervention", "question": "Are other active ingredients or exercise packages separated from the NR-versus-placebo comparison?", "needed": "Full product composition and rules for exercise, rehabilitation, diet, and active-ingredient use in both groups", "role": "Required", "role_reason": "Needed because differences in other active ingredients or rehabilitation may be mixed with the planned contribution of NR.", "application_exception": "The comparison can be retained even when common care is present if its role in both groups is verified. Do not assume that all concomitant interventions were absent.", "criterion": "Verify that the selected contrast is the difference between NR and placebo; do not attribute combined active ingredients or differences in exercise between groups to NR alone.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Specify standard care in both groups and record differences in exercise or rehabilitation, or design these as a separate factor, to estimate the NR contrast.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The question requires an NR-versus-placebo contrast. The principle of not transferring effects from NMN, nicotinamide, niacin, resveratrol, or an exercise package is specified, but full product composition and common care have not been verified.", "condition_status": "Partly verified", "status_reason": "The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure.", "missingness": "The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure.", "uncertainty": "The contrast to be selected is defined, but the actual plan's full composition and concomitant-intervention rules remain unverified. Requesting a single-component contrast differs from having implemented single-component exposure.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Full product composition and rules for exercise, rehabilitation, diet, and active-ingredient use in both groups" }, { "item_id": "N04", "question_type": "Frail population", "question": "Are the criteria of age 75 or older and Fried score 3 or higher, and the population actually selected, verified?", "needed": "Full eligibility criteria, selection flow, Fried components, and actual baseline characteristics table", "role": "Required", "role_reason": "Needed to avoid confusing older age alone, prefrailty, MCI, or PAD with the fixed frailty criteria.", "application_exception": "If data from a mixed population are available, retain the definition of the frail subgroup and its separate results. Do not discard results from other populations or combine them as direct results.", "criterion": "Distinguish the plan's age and frailty criteria read in the official index from whether the population actually recruited and analyzed matches those criteria.", "basis": "M03 §3.2.1; detailed population conditions are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Record the actual selection criteria, baseline Fried components, and comorbidities, and link the analysis denominator for the frail population of interest.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The official registration index records criteria of community dwelling, age 75 or older, and a Fried Frailty Phenotype score of 3 or higher. The relationship between the investigator page's description of mild-to-moderate frailty, detailed exclusion criteria, and the population actually selected is unverified.", "condition_status": "Partly verified", "status_reason": "The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established.", "missingness": "The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established.", "uncertainty": "The criteria are a description of the plan verified from a limited official index. The full registration and actual baseline table cannot be verified from the retained summary currently held, so a match with the actual population is not established.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Full eligibility criteria, selection flow, Fried components, and actual baseline characteristics table" }, { "item_id": "N05", "question_type": "Baseline status", "question": "Are baseline usual speed, nutrition, and deficiency status verified?", "needed": "Data on baseline gait speed, nutrition and dietary assessment, deficiency testing, medications, and walking aids", "role": "Required", "role_reason": "Needed to avoid interpreting results from people with different baseline function or nutritional status as having the same scope of applicability.", "application_exception": "Do not newly impose a deficiency-treatment condition on a trial that did not select participants for deficiency. Retain deficiency status as unverified.", "criterion": "Verify the actual baseline speed and nutrition-related selection criteria; do not substitute deficiency correction or healthy-participant results for this frailty question.", "basis": "M03 §3.2.1; detailed population conditions are internally designed / M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Specify baseline functional and nutritional measures, and, if an effect-modification analysis is needed, prespecify its rationale and analysis plan.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Upper and lower limits for baseline usual gait speed, nutritional status, dietary NR/NAD precursors, and deficiency tests are unverified. The label frailty alone does not establish NR deficiency.", "condition_status": "Unverified", "status_reason": "Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status.", "missingness": "Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status.", "uncertainty": "Values related to baseline speed and deficiency in the original assessment question's identity are null. Data are unavailable to distinguish applicability according to the degree of baseline impairment and nutritional status.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Data on baseline gait speed, nutrition and dietary assessment, deficiency testing, medications, and walking aids" }, { "item_id": "N06", "question_type": "Planned dose", "question": "Does 2,000 mg/day represent a value for which the actual intake and dosing schedule are also verified?", "needed": "Amount per dose, frequency, dose escalation, basis for salt conversion, and actual medication-taking and adherence records", "role": "Required", "role_reason": "Needed because confusing the nominal dose with the exposure actually received changes how efficacy and safety apply.", "application_exception": "Do not calculate a new mass or salt conversion or an optimal dose. Distinguish information that may exist in the original paper from what remains unverified in the current input.", "criterion": "Distinguish the daily amount in the reported plan from actual exposure; do not invent an unknown amount per dose or adherence level.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "In the trial, collect records of each administration and adherence, discontinuations, and dose reductions, and distinguish the prespecified effect of assignment from analyses of actual exposure.", "current_reports": [ "S01" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "NADage's 2,000 mg/day is the planned daily NR amount. Amount per dose, daily frequency, dose escalation, basis for salt conversion, and actual intake are unverified. The conversion to 2 g/day in the original historical calculation is only a cross-check of mass units.", "condition_status": "Partly verified", "status_reason": "The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount.", "missingness": "The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount.", "uncertainty": "The planned daily amount is retained, but it is not actual exposure. The unit conversion also does not verify equivalence in salt or active-moiety amount.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Amount per dose, frequency, dose escalation, basis for salt conversion, and actual medication-taking and adherence records" }, { "item_id": "N07", "question_type": "Planned duration", "question": "Is the 52-week plan linked to actual exposure, measurement, and follow-up after discontinuation?", "needed": "Records of actual initiation, discontinuation, the week 52 visit, observation windows, and follow-up after discontinuation", "role": "Required", "role_reason": "Needed to distinguish the original question's change at 52 weeks from short-term effects or effects after discontinuation.", "application_exception": "Do not make all post-treatment follow-up studies mandatory for the current question. Separate the 52-week result from a distinct claim of persistence.", "criterion": "Do not turn the planned 52 weeks of treatment and assessment into actual visits or a subsequent maintenance effect.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M03 §3.2.1–3.2.4; details concerning dose, persistence, and effect modification are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Record visit windows, actual days of exposure, and missing data appropriate to the original question; if persistence is a separate objective, design follow-up after discontinuation separately.", "current_reports": [ "S01" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The plan specifies 52 weeks of treatment and assessment at week 52. Actual exposure duration and separate follow-up after discontinuation are unverified. The original gait-speed result at that time point is also unverified.", "condition_status": "Partly verified", "status_reason": "The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist.", "missingness": "The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist.", "uncertainty": "The planned duration is known, but actual completion, exposure, and measurement times are unavailable. The plan cannot be read as evidence that long-term results or a maintenance effect exist.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Records of actual initiation, discontinuation, the week 52 visit, observation windows, and follow-up after discontinuation" }, { "item_id": "N08", "question_type": "Placebo comparison", "question": "Are the placebo composition, matching method, and common care in both groups verified?", "needed": "Placebo composition, appearance/sensory matching, and rules for common medications, diet, exercise, and rehabilitation", "role": "Required", "role_reason": "The actual content of the control must be clear to distinguish NR's contribution to the comparison from influences on measurement.", "application_exception": "Do not conclude that an unverified composition means the placebo was absent or blinding failed.", "criterion": "Distinguish the existence of a placebo plan from verification of the actual composition, blinding, and common care.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptation are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Disclose the placebo and common care, and record blinding for medication taking and assessment and differences in care between groups.", "current_reports": [ "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The official registration index describes a placebo-comparison plan. The fields for the placebo's exact composition, matching method, and common care in both groups are null or unverified.", "condition_status": "Partly verified", "status_reason": "The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented.", "missingness": "The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented.", "uncertainty": "The comparator's name is verified, but it cannot be verified whether NR was the only actual difference or how blinding was implemented.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Placebo composition, appearance/sensory matching, and rules for common medications, diet, exercise, and rehabilitation" }, { "item_id": "N09", "question_type": "Allocation implementation", "question": "Are the actual implementation and concealment of the randomized, double-blind plan verified?", "needed": "Full protocol, allocation-sequence generation/concealment, and data on actual allocation and baseline balance", "role": "Required", "role_reason": "Needed because the label of a planned RCT alone does not establish that an actual causal comparison was implemented.", "application_exception": "Do not replace an unverified design status with nonapplicability of crossover or cluster designs. Retain the plan and actual implementation separately.", "criterion": "Distinguish the design label from actual allocation implementation; do not describe unverified implementation as actual nonimplementation.", "basis": "M08 §8.1–8.2.3; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Document the actual allocation sequence, concealment, blinding, and baseline characteristics, and report results for the selected effect of assignment.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "S01–S02 are retained as a randomized, double-blind, placebo-controlled plan. The full registration, actual allocation, concealment, baseline balance, and data on actual implementation and results have not been verified.", "condition_status": "Partly verified", "status_reason": "The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed.", "missingness": "The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed.", "uncertainty": "The design description in the public plan alone does not verify the actual allocation process. Do not reassess unknown implementation as either unbiased or failed.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Full protocol, allocation-sequence generation/concealment, and data on actual allocation and baseline balance" }, { "item_id": "N10", "question_type": "Measurement of usual speed", "question": "Are the test distance, acceleration section, repetitions, and instrument for usual speed verified?", "needed": "Usual-speed measurement manual, walking aids, assessors, repetitions, and unit definitions", "role": "Required", "role_reason": "Needed to prevent differences in measurement methods from being mixed with actual functional change.", "application_exception": "Do not assume measurement is free of problems because the test is objective. Do not declare that information is unreported throughout the original source merely because it is absent from the plan.", "criterion": "Verify the actual m/s test method for habitual/comfortable pace; do not substitute maximal speed or endurance speed.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Standardize the usual gait-speed procedure and specify assessment time points, aids, assessor blinding, and repeated measurements.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The question concerns change in m/s at a usual, comfortable pace. The actual test distance, acceleration section, instrument, repetitions, walking aids, and assessor blinding are unverified.", "condition_status": "Unverified", "status_reason": "target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical.", "missingness": "target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical.", "uncertainty": "target_endpoint defines the measurement concept for the question, but protocol_details is null. Matching units or the word gait alone does not establish that the tests are identical.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Usual-speed measurement manual, walking aids, assessors, repetitions, and unit definitions" }, { "item_id": "N11", "question_type": "6-minute-walk boundary", "question": "Is NADage's 6-minute walk with concurrent sensors the same endpoint as usual speed over a short course?", "needed": "Definitions of the 6-minute walk/sensors and data on equivalence with the usual-speed test and separately reported results", "role": "Required", "role_reason": "This is a key endpoint condition for upgrading the closest study to direct evidence of the effect.", "application_exception": "Do not deem it equivalent to comfortable walking over a short course merely because sensors collect speed.", "criterion": "Do not currently equate the planned 6-minute walk with usual gait speed; require actual verification of equivalence or a separate result.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is internally designed / M08 Table 8.2.a, M03 §3.2.4; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Measure the two tests separately, describe their protocols, units and observation windows, and report a usual gait speed estimate that matches the question.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The public plan for NADage, the closest study, describes a 6-minute walk with concurrent sensor gait assessment. Whether this is an endpoint equivalent to usual short-course gait speed has not been verified.", "condition_status": "Partly verified", "status_reason": "The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap.", "missingness": "The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap.", "uncertainty": "The endpoint's actual name in the plan is verified, but usual_gait_equivalence is not_verified. Creating usual gait speed from distance÷time does not resolve this gap.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Definitions of the 6-minute walk/sensors and data on equivalence with the usual-speed test and separately reported results" }, { "item_id": "N12", "question_type": "Endpoint hierarchy", "question": "Are the page's usual gait speed endpoint and its actual trial hierarchy as primary, secondary or post hoc verified?", "needed": "The hierarchy of usual gait speed and reasons for changes in dated registration histories, protocols and analysis plans", "role": "Required", "role_reason": "The editor's chosen question must be distinguished from the original trial's prespecified outcome selection.", "application_exception": "Do not treat failure to acquire the registration history as confirmation of nonregistration or selective reporting.", "criterion": "Do not turn the page's single primary endpoint and the investigator page's description of the 6-minute walk as primary into a primary usual gait speed outcome within the trial.", "basis": "M08 Table 8.2.a, M04 §4.6.3; project-specific application / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Specify the hierarchy and analysis of usual gait speed in the advance plan, and compare the reasons for changes in the actual report together with their dates.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Usual gait speed is this page's single editorial endpoint. The investigator page describes the 6-minute walk and sensor assessment as primary, but the field for the hierarchy of usual gait speed within the actual trial is null.", "condition_status": "Partly verified", "status_reason": "The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified.", "missingness": "The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified.", "uncertainty": "The two descriptions concern different things, so this alone is not designated a data conflict. The prespecified hierarchy and analysis plan for usual gait speed, and their agreement with the actual report, remain unverified.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The hierarchy of usual gait speed and reasons for changes in dated registration histories, protocols and analysis plans" }, { "item_id": "N13", "question_type": "Planned sample", "question": "Are the planned 100 participants distinguished from the actual enrolled, randomized, completed and usual gait speed analysis counts?", "needed": "Participant flow diagram; enrollment, allocation and completion by group; usual gait speed analysis denominators and reasons for exclusion", "role": "Required", "role_reason": "This is needed to avoid claiming precision of an effect or completion on the basis of a planned number.", "application_exception": "Do not create a recruitment status or analysis count at the cutoff solely from historical wording that enrollment had actually begun.", "criterion": "Do not use planned enrollment as the outcome analysis n; link the actual denominators at each stage.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Report the actual sample flow at each stage, the corresponding usual gait speed analysis n and reasons for missingness alongside the results.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "NADage's 100 participants are a planned count. Actual enrollment, randomization, completion and usual gait speed analysis counts remain unverified.", "condition_status": "Partly verified", "status_reason": "The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator.", "missingness": "The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator.", "uncertainty": "The nature of the planned n is clear, but actual sample-flow data are unavailable. The 100 participants cannot be converted into a per-group n or an analysis denominator.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Participant flow diagram; enrollment, allocation and completion by group; usual gait speed analysis denominators and reasons for exclusion" }, { "item_id": "N14", "question_type": "Current registry status", "question": "Can the latest recruitment and results-posting status as of the reference date be verified?", "needed": "NCT06208527 registration history, status and posted results documents as of the relevant reference date", "role": "Required", "role_reason": "This is needed to avoid wrongly attributing generic wording on the registry screen to the trial's actual progress.", "application_exception": "Distinguish the current status of access not attempted from the failure to acquire the body text at that earlier time. Do not use a valid response with 0 results or an unverified status to mean that research does not exist.", "criterion": "Distinguish the historical description of recruitment starting and the registry index from the actual status/posted results as of the reference date.", "basis": "M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are project-specific / M04 §4.5, §4.6.3; limits on conversion of current materials follow the user's scope and project-specific design / M08 Table 8.2.a, M04 §4.6.3; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Verification of suitable materials means linking registry versions and results documents to their dates at the time; it is distinct from conducting a new trial itself.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The wording on the investigator page about recruitment starting is a historical record. S02's directly accessed body was a glossary-only application shell, and the latest status, registration history and posted results were not verified at that time.", "condition_status": "Unverified", "status_reason": "The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist.", "missingness": "The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist.", "uncertainty": "The registry was not accessed in the current work. Do not read the generic word Withdrawn in the shell seen at that time as this trial's withdrawal status, or conclude that no latest results exist.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "NCT06208527 registration history, status and posted results documents as of the relevant reference date" }, { "item_id": "N15", "question_type": "Effect of interest", "question": "Are the actual between-group analysis, ITT/PP and adjustment for usual gait speed verified?", "needed": "Documents defining the estimand of interest, analysis population, model, adjustment and actual results", "role": "Required", "role_reason": "This is needed to avoid treating within-group change, the effect of adherence and the planned effect of assignment as the same actual between-group value.", "application_exception": "Do not fill unverified analysis information with an arbitrary ITT, complete-case or PP analysis.", "criterion": "Distinguish the question of the NR−placebo effect of assignment on change from baseline to 52 weeks from the actual analysis.", "basis": "M08 §8.2.2, M15 §15.3.1; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Prespecify the effect of interest, handling of missingness and adherence, and adjustment in the analysis plan, and report an estimate for that contrast.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The question concerns the between-group difference in change in usual gait speed from baseline to 52 weeks under treatment assignment. The actual analysis population, ITT/PP, adjusted model and results remain unverified.", "condition_status": "Unverified", "status_reason": "The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial.", "missingness": "The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial.", "uncertainty": "The estimand in the original question identity is the requested question. It cannot automatically be elevated to an analysis performed in the actual trial.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Documents defining the estimand of interest, analysis population, model, adjustment and actual results" }, { "item_id": "N16", "question_type": "Missingness and attrition", "question": "Who was missing from the 52-week speed measurement, and how was this handled?", "needed": "Missed visits, discontinuation, death/illness, inability to measure, handling of missingness and sensitivity analyses by group", "role": "Required", "role_reason": "This is needed to distinguish values from only those with measured outcomes from the effect of assignment during long-term observation of frail participants.", "application_exception": "Do not turn the possibility of missingness into a confirmed magnitude of actual bias or a finding that the trial is invalid.", "criterion": "Link actual measurement and analysis denominators to reasons for missingness; do not turn unverified information into no attrition or 0 events.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific / M08 §8.2.2, M15 §15.3.1; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Report visit flow, including discontinuation, death and inability to measure, together with prespecified handling of missingness and sensitivity analyses.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Actual completion and usual gait speed analysis counts and the reasons for missing measurements are not verified in the retained materials. Observation losses cannot be assessed solely from the planned 52 weeks and 100 participants.", "condition_status": "Unverified", "status_reason": "Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged.", "missingness": "Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged.", "uncertainty": "Without actual sample flow and analysis data, the adequacy of missing-data handling or completeness of follow-up cannot be judged.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Missed visits, discontinuation, death/illness, inability to measure, handling of missingness and sensitivity analyses by group" }, { "item_id": "N17", "question_type": "Target effect estimate", "question": "Are direct usual gait speed changes, the between-group difference and CI verified?", "needed": "Group-specific original usual gait speed values/changes, between-group estimate and CI for the fixed population, exposure and time point", "role": "Required", "role_reason": "This is a key condition for distinguishing the existence of direct results from plans and adjacent numerical findings.", "application_exception": "Do not convert distance, within-group P values or NAD values into a direct between-group effect in m/s.", "criterion": "Link the m/s result corresponding to the original question; if absent, leave the value null.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific / M15 §15.3.1–15.3.3; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "An eligible study reports group-specific results for the defined usual gait speed test together with the estimate, CI and denominator for the selected contrast.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The original values, changes, between-group estimate and CI for directly eligible usual gait speed remain unverified. target_between_group_effect_mps and target_ci are null.", "condition_status": "Unverified", "status_reason": "The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent.", "missingness": "The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent.", "uncertainty": "The currently retained materials include plans and results for other questions. Failure to verify direct results does not mean that the effect is 0 or that all human research is absent.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Group-specific original usual gait speed values/changes, between-group estimate and CI for the fixed population, exposure and time point" }, { "item_id": "N18", "question_type": "Variance and intervals", "question": "Are the SD, SE, covariance and interval type for the target change verified?", "needed": "Variance type, analysis n and model for usual gait speed change, and the reported between-group interval", "role": "Required", "role_reason": "This is needed to avoid creating a nonexistent interval by combining numerical values with different variance types or targets.", "application_exception": "Do not use an assumed variance in a plan as an actually observed variance. Do not make a broad declaration of nonreporting by saying it is absent from the original text either.", "criterion": "Use only variance and intervals belonging to the direct result; do not import SD or a one-sided CI from another trial.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptation by study design is project-specific / M15 §15.3.1–15.3.3; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Disclose the variance type, denominator, interval construction and analysis model for the relevant usual gait speed result.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The analysis denominator and CI for the target result remain unverified. The manuscript states that it did not estimate or fill in the target CI, SD, SE or covariance.", "condition_status": "Unverified", "status_reason": "No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint.", "missingness": "No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint.", "uncertainty": "No observed variance is available for calculating a new standardized effect or precision. The one-sided 90% interval from PAD pertains to a different endpoint.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Variance type, analysis n and model for usual gait speed change, and the reported between-group interval" }, { "item_id": "N19", "question_type": "Clinical importance", "question": "Is a clinically important between-group difference appropriate to this frail population and test verified?", "needed": "Evidence for a clinically important between-group difference for the relevant frail population and usual gait speed protocol", "role": "Required", "role_reason": "This is needed to avoid equating nominal statistical significance with a clinically important improvement in usual gait speed.", "application_exception": "Because the usual gait speed value itself is the original question, do not impose a separate mortality trial as a prerequisite for that value.", "criterion": "Distinguish statistical success from clinical importance, and do not set an unsupported common MCID, minimum participant count or duration.", "basis": "M15 §15.3.1–15.3.3; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "First justify the evidence for an important difference appropriate to the population, test and between-group contrast, then interpret it alongside the estimated interval.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The applicable between-group MCID field is null. The original question separately requires a valid between-group estimate and an interpretation of clinical importance appropriate to the population and test.", "condition_status": "Unverified", "status_reason": "The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either.", "missingness": "The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either.", "uncertainty": "The clinical importance for this question cannot be determined from another gait test, a threshold for individual change or a planned participant count. Exclusion of an important benefit has not been verified either.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Evidence for a clinically important between-group difference for the relevant frail population and usual gait speed protocol" }, { "item_id": "N20", "question_type": "Funding and provision", "question": "Are the plan's funding, product provision and authors' conflicts of interest directly verified?", "needed": "NADage's original funding information, product provision, author roles, and patent/employment/declared conflicts of interest", "role": "Supplementary; required for a claim of independence", "role_reason": "This is needed to avoid inferring independent funding or manufacturer involvement from an unverified supply chain.", "application_exception": "Do not exclude a result solely because a conflict of interest exists. Do not use unverified information as evidence of independence.", "criterion": "Separate the existence of a funding description from full verification of provision/conflicts of interest, and do not assign an independence score to a missing result.", "basis": "Chamgap's own conditions for independence and attribution. The official methods sections used in this pilot do not endorse all of these detailed items", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Link funding, product provision and author roles to the results data, and verify the actual study families when claiming independent replication.", "current_reports": [ "S01" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The record that S01 contains funding information and the relevant location are retained. Because no directly eligible result has been verified, the original independence axis is null. This retained summary contains no extracted values for the specific funding source, product provision or all author roles, so their content was not inferred.", "condition_status": "Partly verified", "status_reason": "The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information.", "missingness": "The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information.", "uncertainty": "The existence and location of funding information are recorded, but the level of actual content in the current input is limited. Do not copy ChromaDex relationships from other NR trials as NADage's provision information.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "NADage's original funding information, product provision, author roles, and patent/employment/declared conflicts of interest" }, { "item_id": "N21", "question_type": "Studies and reports", "question": "Are plans, papers, registrations and corrections kept from being double-counted as independent trials of effect?", "needed": "A mapping of report identifiers, native F01–F05 relationships, and eligible results/endpoints/time points", "role": "Required", "role_reason": "This is needed to avoid erasing gaps by counting materials as human trials or replication confirmations.", "application_exception": "If bibliographic details or report families are unresolved, retain provisional relationships and omissions; do not create new reports.", "criterion": "Group the investigator page and registration for the same plan, and papers/corrections for the same trial, leaving unresolved unique trial and participant counts null.", "basis": "M04 §4.6.1–4.6.2 distinction between studies and reports; cohort/outcome linkage is a project-specific application / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "When collecting materials, verify the relationships between registration numbers/DOIs and results/time points/analyses to link multiple reports of the same study.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S08", "S09", "S10" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The native evidence distinguishes NADage F01, NR-VETS F02, Orr MCI F03, the healthy-adult crossover F04 and NICE PAD F05. S01–S02, S03–S04 and S09–S10 are related reports within their respective families; retain the narrow original record that the number of directly eligible results is 0.", "condition_status": "Partly verified", "status_reason": "The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created.", "missingness": "The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created.", "uncertainty": "The 5 family descriptions and 15 actual citations record existence; they are not counts of direct usual gait speed trials or unique participants. Within the S05–S07 range notation in evidence, individual S06/S07 citations are absent from the current list and must not be created.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "A mapping of report identifiers, native F01–F05 relationships, and eligible results/endpoints/time points" }, { "item_id": "N22", "question_type": "Adjacent trial in prefrailty", "question": "Is the NR-VETS population the same as the selected frail population with Fried scores of 3 or higher?", "needed": "Complete NR-VETS eligibility criteria, amendment history and usual gait speed results by frailty stratum", "role": "Required", "role_reason": "This is needed to avoid repurposing prefrail or non-frail results as direct results for the target frail population.", "application_exception": "Reconsider eligibility if the latest complete registration is acquired and shows population amendments or separate results.", "criterion": "Distinguish the Fried<3 description in the currently retained official institutional index from the selected frailty criterion, leaving the latest amendments or target-stratum results unverified.", "basis": "M03 §3.2.1; detailed population conditions are project-specific / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Verify separate results by frailty stratum in that study, or perform the same usual gait speed comparison in the selected Fried≥3 population.", "current_reports": [ "S03", "S04" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The institutional index for NR-VETS describes non-frail and prefrail participants, Fried<3. This does not match the Fried≥3 population criterion for this question, and the complete protocol and target results remain unverified.", "condition_status": "Not met", "status_reason": "The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established.", "missingness": "The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established.", "uncertainty": "The population described in the currently retained index differs from the fixed question. This does not mean that NR-VETS has no efficacy or that exclusion of frail participants across all amended versions has been established.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Complete NR-VETS eligibility criteria, amendment history and usual gait speed results by frailty stratum" }, { "item_id": "N23", "question_type": "Within-group MCI results", "question": "Are Orr's two p-values a between-group effect on usual gait speed in frail participants?", "needed": "Orr's gait test, actual between-group m/s estimate/CI and results tables by population", "role": "Required", "role_reason": "Within-group contrasts must be distinguished from an actual between-group difference.", "application_exception": "Retain within-group p-values as original adjacent results, but do not calculate a new difference or CI.", "criterion": "Do not read the respective within-group p-values for placebo and NR as a between-group test or a result for the target frail population.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is project-specific / M08 §8.2.2, M15 §15.3.1; project-specific application / M04 §4.6.1–4.6.2, M15 §15.3.1; project-specific application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Report a direct between-group estimate appropriate to the population of interest and usual gait speed test, and distinguish it from within-group results.", "current_reports": [ "S05" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "In Orr MCI, placebo p=0.0402 and NR p=0.4698 are tests of within-group walking-speed change in each group. They are not a between-group effect in m/s, and the clinical MCI eligibility criteria differ from the frailty eligibility conditions for this question.", "condition_status": "Not met", "status_reason": "A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results.", "missingness": "A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results.", "uncertainty": "A difference in significance between the two within-group tests is not a test of the between-group effect. The target population, protocol and between-group estimate have not been verified, so these cannot be used as direct results.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Orr's gait test, actual between-group m/s estimate/CI and results tables by population" }, { "item_id": "N24", "question_type": "MCI denominators and schedule", "question": "Are Orr's actual completion count, gait analysis denominator and dosing schedule verified?", "needed": "Orr’s participant flow by stage, gait-analysis n, dose escalation/treatment days, and data for the target frail population", "role": "Required", "role_reason": "Needed to prevent the completed counts and schedules of adjacent trials from being imported as the exposure and denominator for the direct question.", "application_exception": "Detailed counts that may appear in another retained assessment of the same Orr family are not automatically imported into this manuscript.", "criterion": "Do not repurpose the 20 completers or descriptions of schedules from other trials as the analysis denominator or 52-week duration for the target usual gait speed.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "For adjacent evidence, verify the actual participant flow and analysis denominator in its original table; assess the target comparison using a separate eligible population and 52-week results.", "current_reports": [ "S05" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Orr’s abstract and figure captions record 20 completers. The total number randomized and the gait-outcome analysis denominator are unverified in this manuscript. The historical calculation cross-checking the phases 1+1+1+6 against 9 weeks records ambiguity in the abstract’s duration wording; it does not constitute a correction of the original table or a target 52-week result.", "condition_status": "Partly verified", "status_reason": "Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days.", "missingness": "Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days.", "uncertainty": "Only the completed count and a cross-check of the historical schedule are available; an analysis count for the target population is absent. That calculation is not presented as a new clinical calculation or as confirmed actual treatment days.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Orr’s participant flow by stage, gait-analysis n, dose escalation/treatment days, and data for the target frail population" }, { "item_id": "N25", "question_type": "Healthy-participant crossover", "question": "Are Martens’ motor-function results in healthy participants equivalent to the target frailty comparison?", "needed": "Exposure, duration, baseline function, usual-speed results, and crossover analysis in the healthy-participant crossover trial", "role": "Required", "role_reason": "Needed to retain the existence of contrary results while preventing refutation in a different population from being transferred to this question.", "application_exception": "Retain the original crossover design, but do not estimate the paired variance for the target usual speed from these data.", "criterion": "Do not aggregate statements of no difference in motor function among healthy participants as repeated refutations of the target frailty comparison.", "basis": "M03 §3.2.1; detailed population criteria are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M08 §8.2.2, M15 §15.3.1; internal application / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Verify results using the same frail population, exposure, and test; when using crossover data, report period, sequence, and carryover effects and a paired analysis.", "current_reports": [ "S08" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Martens’ crossover trial in healthy middle-aged and older adults reported no improvement in overall motor function. Baseline function and the regimen differ, and no target usual-speed values were reconstructed from the supplementary motor-function figures.", "condition_status": "Not met", "status_reason": "The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0.", "missingness": "The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0.", "uncertainty": "The population and regimen differ from the fixed question of frailty, 2,000 mg/day, and 52 weeks. The adjacent trial’s no-difference result is retained, but it is not used as evidence that the target effect is 0.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Exposure, duration, baseline function, usual-speed results, and crossover analysis in the healthy-participant crossover trial" }, { "item_id": "N26", "question_type": "Positive PAD result", "question": "Is NICE’s +17.6 m an effect on usual gait speed in m/s in the frail population?", "needed": "NICE’s original 6-minute-walk table and separate usual-speed results for the selected frail population", "role": "Required", "role_reason": "Needed to retain positive adjacent results without elevating them to direct efficacy evidence.", "application_exception": "Attribute the original +17.6 m and the historical 7.0−(−10.6) cross-check only to that PAD distance result.", "criterion": "Retain the positive 6-month result for 6-minute walk distance in its original unit, population, and contrast; do not divide by time to create a usual-speed result.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Measure usual speed separately in the target frail population and report the selected contrast, time point, and denominator.", "current_reports": [ "S09" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "NICE PAD randomized 90 participants overall. The 6-month between-group result for 6-minute walk distance, +17.6 m, is a positive adjacent result. WIQ speed is a self-reported score; these values are not usual-gait-speed results in m/s for the target frail population.", "condition_status": "Not met", "status_reason": "The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time.", "missingness": "The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time.", "uncertainty": "The positive signal is retained, but the population, endpoint, and time point differ from the fixed question. Do not use the 90 randomized overall as the analysis n for the target speed or calculate distance÷time.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "NICE’s original 6-minute-walk table and separate usual-speed results for the selected frail population" }, { "item_id": "N27", "question_type": "PAD interval and criterion", "question": "Are NICE’s one-sided 90% CI and p=0.08 distinguished from its study-specific criterion?", "needed": "NICE’s prespecified statistical criterion, definition of the one-sided interval, and location of the original between-group report", "role": "Required", "role_reason": "Needed to avoid changing the meaning by misrepresenting the adjacent study’s interval type and study-specific criterion.", "application_exception": "Do not calculate a new two-sided CI, standardized effect, or MCID. Verify only at the level of the explanation in the manuscript at that time.", "criterion": "Do not convert the reported one-sided 90% interval’s lower bound and open upper bound +∞, or p=0.08, into a two-sided 95% interval or a CI in the target m/s unit.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed / M15 §15.3.1–15.3.3; internal application / M08 Table 8.2.a, M04 §4.6.3; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Future direct studies should disclose the prespecified statistical criterion, interval type, and contrast of interest alongside the results, distinguishing these from clinical importance.", "current_reports": [ "S09" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "NICE’s adjacent distance result is a one-sided 90% CI [+1.77,+∞) m and p=0.08. The manuscript explains that it met the study’s prespecified significance criterion. It was not reclassified as a failure under a universal p<.05 criterion.", "condition_status": "Verified", "status_reason": "The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified.", "missingness": "The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified.", "uncertainty": "The manuscript retains the interval type, lower bound, open upper bound, and explanation of the study-specific criterion. This does not mean that statistical or clinical success for the target usual speed has been verified.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "NICE’s prespecified statistical criterion, definition of the one-sided interval, and location of the original between-group report" }, { "item_id": "N28", "question_type": "Scope of the correction notice", "question": "Are the actual content of the NICE correction notice and its impact on the results verified?", "needed": "The original article’s change history, the full correction notice, and links between results/tables before and after the correction", "role": "Required", "role_reason": "Needed to prevent bibliographic information about a correction from being overstated as a review of its content or verification of changes to results.", "application_exception": "Do not label the lack of an attempt this time as an actual access failure at that earlier time.", "criterion": "Distinguish the correction notice’s existence/DOI from its content, and do not speculate about what was corrected.", "basis": "M04 §4.5–4.6 principles for data collection/selection; separation of access from reading and the hyperlink contract are internally designed / M04 §4.5, §4.6.3; limits on conversion to current materials derive from the user-defined scope and internal design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "When reviewing materials, compare what the full correction notice changes with the original table and record it. This is a verification task distinct from designing a new clinical trial.", "current_reports": [ "S09", "S10" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The record states that the existence and identifier of the 2024-08-12 NICE publisher correction were verified in the original article’s change history. The content of the correction notice was not acquired at that time.", "condition_status": "Partly verified", "status_reason": "The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate.", "missingness": "The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate.", "uncertainty": "The existence of the correction notice is retained, but its body, what was changed, and its impact on the results are unverified. Do not automatically describe it as a retraction or a correction to an effect estimate.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The original article’s change history, the full correction notice, and links between results/tables before and after the correction" }, { "item_id": "N29", "question_type": "Other molecules", "question": "Are NMN, NAM, niacin, and tryptophan materials evidence for NR alone?", "needed": "The actual active ingredient, product composition, endpoint, and population identity of candidate studies", "role": "Required", "role_reason": "Needed to prevent distinct exposures from being merged under the collective term NAD precursors.", "application_exception": "Do not elevate a record of screening the substance from the title to verification of the full product composition or reading of the full results text.", "criterion": "Do not use other molecules as synonyms for NR, and do not change nicotinamide in the NICE-FIT title to NR.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "When checking study eligibility, verify the active molecule, salt, and composition, and design a separate direct study for the NR question.", "current_reports": [ "S13", "S14", "S17" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "S13 concerns tryptophan, nicotinic acid, and nicotinamide; S14 concerns NMN. The S17 NICE-FIT title contains nicotinamide. Candidates not verified as NR are not used as direct NR evidence.", "condition_status": "Not met", "status_reason": "The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs.", "missingness": "The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs.", "uncertainty": "The retained substance identity differs from the requested NR or is not verified as NR. Positive gait results for NMN also do not verify a direct NR effect because the molecule differs.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The actual active ingredient, product composition, endpoint, and population identity of candidate studies" }, { "item_id": "N30", "question_type": "Combination with exercise", "question": "Is the NR+exercise trial in hypertension a contrast of NR alone for gait speed in frailty?", "needed": "S15’s exercise requirements in both arms, NR contrast, frail stratum, and usual-speed results", "role": "Required", "role_reason": "Needed to avoid confusing the contribution of exercise with that of NR alone.", "application_exception": "Do not state that review of the full results and exercise control is complete on the basis of screening only the publisher’s abstract.", "criterion": "Distinguish the combination with aerobic exercise in participants with hypertension from the target contrast of NR alone versus placebo.", "basis": "M03 §3.2.1; detailed population criteria are internally designed / M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / M04 §4.6.1–4.6.2, M15 §15.3.1; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Specify the exercise common to both arms and the NR difference, or separate their contributions using a factorial design, and measure usual speed in the target frail stratum.", "current_reports": [ "S15" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "S15 is a pilot trial of NR+exercise in middle-aged and older adults with hypertension. The record is of screening at the level of the publisher’s abstract and bibliographic back matter; it was not counted as a direct replication of usual-speed results in the target frail population.", "condition_status": "Not met", "status_reason": "The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified.", "missingness": "The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified.", "uncertainty": "The population and concurrent intervention in the screening record differ from the fixed question. Separation of exercise by arm and the target speed results were not verified.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "S15’s exercise requirements in both arms, NR contrast, frail stratum, and usual-speed results" }, { "item_id": "N31", "question_type": "Species and combination products", "question": "Does the combination-product cognition study in senior dogs address the NR gait question in older humans?", "needed": "S18’s species, active ingredients, and measured outcomes, and direct evidence in humans", "role": "Required", "role_reason": "Needed to prevent automatic attribution of nonhuman, combination-product, and other-function data to this question.", "application_exception": "Retain nonhuman materials as identity-screening records, but do not add them to the count of human trials.", "criterion": "Do not transfer combination-product and owner-assessed cognition results in dogs to usual speed with NR alone in humans.", "basis": "M03 §3.2.1; detailed population criteria are internally designed / M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed / M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "A direct comparison with the target human population, exposure to the single intervention, and a usual-speed test is needed.", "current_reports": [ "S18" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "S18 concerns a senolytic/NAD-precursor combination and owner-assessed cognition in senior dogs. It was excluded at screening because the species, intervention, and endpoint differ, and no dog effect estimates were used.", "condition_status": "Not met", "status_reason": "The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research.", "missingness": "The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research.", "uncertainty": "The actual question in the archived bibliographic record differs from the selected question about gait with NR alone in humans. The title/abstract screening record is not a refutation of human research.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "S18’s species, active ingredients, and measured outcomes, and direct evidence in humans" }, { "item_id": "N32", "question_type": "Mechanism and function", "question": "Are direct usual-speed results verified separately from NAD increases, SPPB, strength, and fatigue?", "needed": "A report distinguishing direct results for the target usual speed from other functional and biochemical results", "role": "Required", "role_reason": "Needed to prevent mechanism and function from automatically being interpreted as the same outcome.", "application_exception": "Because the functional score itself is the original question, do not require separate death events as a prerequisite for that value.", "criterion": "Do not substitute mechanism or other tests for the selected functional endpoint, or vice versa; require direct results for this question.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptations of outcomes to each question are internally designed / M03 §3.2.4; internally defined scope-expansion boundary", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Measure the selected usual speed separately from mechanisms and other functions, and prespecify and report each contrast of interest.", "current_reports": [ "S05", "S08", "S09" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "NAD increases, SPPB, chair rises, strength, fatigue, and usual gait speed are different outcomes. P on the original axis denotes a functional endpoint performed by the patient; it does not mean that a direct effect has been verified.", "condition_status": "Unverified", "status_reason": "Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null.", "missingness": "Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null.", "uncertainty": "Signals from other measures or the existence of a functional-test battery cannot fill in the between-group difference for the target usual speed. That direct value is currently null.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "A report distinguishing direct results for the target usual speed from other functional and biochemical results" }, { "item_id": "N33", "question_type": "Harms for the target question", "question": "Are events, discontinuations, and denominators verified for this plan in the frail population at 2,000 mg/day for 52 weeks?", "needed": "Arm-specific AE/SAE, numbers of people and events, discontinuations, collection periods, and collection methods for the same population, product, and exposure", "role": "Supplementary; required for expansion to safety", "role_reason": "Needed to prevent data gaps from being elevated to a guarantee of safety or confirmation of NR harm.", "application_exception": "Even if a signal without a denominator is added, do not convert it into an incidence rate; retain separate efficacy and harm statuses.", "criterion": "Distinguish an efficacy plan from direct safety data, and do not record unverified events as 0 or as confirmation of safety.", "basis": "M19 §19.1.2–19.2.4; internal application / M19 §19.1.2–19.2.4; detailed distinctions are internally designed / M19 §19.2 harm questions by study design; details of temporal relationships are internally designed / M19 §19.2.2–19.2.4, M03 §3.2.3; internal application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / M19 §19.1.2–19.2.4, M04 §4.6.3; internal application / Chamgap’s own interpretive boundary. References M19 principles; not an application of an official causality tool", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "In long-term comparisons, collect event definitions, collection schedules, discontinuations, exposure time, concomitant treatments, and arm-specific numbers of people and events. Consider follow-up designs suited to rare events separately.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Adverse events, discontinuations, and long-term safety are unverified for the high-dose, long-term plan in the target frail population. Caution in the original safety label does not mean that NR harm has been established.", "condition_status": "Unverified", "status_reason": "Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data.", "missingness": "Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data.", "uncertainty": "Event frequency or causality cannot be assessed because records are absent for event definitions, systematic/spontaneous collection, exposure denominators, temporal order, discontinuation/recovery, between-arm comparisons, other causes, and missing data.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Arm-specific AE/SAE, numbers of people and events, discontinuations, collection periods, and collection methods for the same population, product, and exposure" }, { "item_id": "N34", "question_type": "Scope of official safety assessments", "question": "Does EFSA’s assessment of specified NR chloride for use at 300 mg/day in healthy adults guarantee safety for the target question?", "needed": "The substance, use amount, population, and duration in the EFSA assessment, and direct safety data from the target trial", "role": "Supplementary; required for expansion to safety", "role_reason": "Needed to avoid extending the authority of an official assessment to a guarantee of safety for all other exposures.", "application_exception": "Official documents are not independent new events or trials; do not double-count safety data they cite again. Do not use a use assessment as personal dosing instructions.", "criterion": "State the scope of the official use assessment, and do not transfer assessments of different substances, doses, or populations to the overall safety of the target plan.", "basis": "M19 §19.1.2–19.2.4; internal application / M04 §4.6.1–4.6.2; adaptations of harm data are internally designed / Chamgap’s own interpretive boundary. References M19 principles; not an application of an official causality tool", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Separately review long-term safety follow-up appropriate to the target product, dose, and frail population, along with data on concomitant treatments and vulnerable groups.", "current_reports": [ "S11", "S12" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "S11/S12 are official safety and use assessments of specified NR chloride. Assessment of use at 300 mg/day in healthy adults is neither a safety guarantee for this frail population’s plan of 2,000 mg/day for 52 weeks nor approval of walking efficacy.", "condition_status": "Not met", "status_reason": "The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR.", "missingness": "The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR.", "uncertainty": "The populations, substances, and conditions of use in the official materials are not equivalent to direct safety information for the target plan. The manuscript also did not copy nicotinic-acid flushing or hepatic harm to NR.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The substance, use amount, population, and duration in the EFSA assessment, and direct safety data from the target trial" }, { "item_id": "N35", "question_type": "Actual concomitant treatments and adherence", "question": "Are arm-specific changes in medicines, diet, exercise, rehabilitation, and dose reduction/discontinuation verified?", "needed": "Lists and timing of concomitant treatments in both arms, medication adherence, dose reduction/discontinuation, rescue treatment, and analytical handling", "role": "Required", "role_reason": "Concurrent exposures, selection, and losses must be distinguished when attributing the actual effect of interest and harms.", "application_exception": "Do not exclude solely because concomitant treatment is present; compare differences between arms, the contrast of interest, and handling methods.", "criterion": "Connect differences in actual exposure and concurrent treatments to interpretation of results and safety, and do not confirm actual implementation from planned rules alone.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; internal application / M19 §19.2.2–19.2.4 design considerations; detailed confounding records are internally designed / M19 §19.1.2–19.2.4, M04 §4.6.3; internal application", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Collect the timing of medication changes and concurrent treatments, and explicitly distinguish the effect of assignment, the effect of adherence, and attribution of harms.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Policies for common medicines, diet, exercise, and rehabilitation in both arms, and actual dosing frequency, dose escalation, adherence, and changes, are unverified. Do not attribute effects of other medicines or rehabilitation to NR.", "condition_status": "Unverified", "status_reason": "The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use.", "missingness": "The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use.", "uncertainty": "The full registration and actual implementation records have not been verified, so the effects of concurrent changes and discontinuations cannot be assessed. Do not fill these gaps with an absence of concomitant treatment or completed medication use.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Lists and timing of concomitant treatments in both arms, medication adherence, dose reduction/discontinuation, rescue treatment, and analytical handling" }, { "item_id": "N36", "question_type": "Extension to dose and persistence", "question": "Does the claim also extend to the optimal dose, maintenance after discontinuation, and effects in other frailty strata?", "needed": "Direct dose comparisons, follow-up after discontinuation, and prespecified subgroup/interaction data needed when making such extended claims", "role": "Supplementary; required for extended claims", "role_reason": "A boundary condition to prevent a narrow result from being extended to optimal treatment, maintenance, or all subgroups.", "application_exception": "Actual 52-week results for the original question are needed. Separate evidence of maintenance effects after discontinuation is not imposed as a mandatory requirement for this table.", "criterion": "Separate the narrow planned contrast from effects at other doses, after discontinuation, and in subgroups; do not require extension trials unnecessary for the current question.", "basis": "M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "If a new extension question is requested, first define separate questions and plans for dose comparisons, follow-up after discontinuation, and effect modification.", "current_reports": [ "S01", "S02" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The current table concerns usual speed under the planned conditions of 2,000 mg/day, 52 weeks, and Fried≥3. It does not establish the optimal dose, persistence after discontinuation, or effects across all frailty strata at the same time.", "condition_status": "Not applicable", "status_reason": "Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read.", "missingness": "Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read.", "uncertainty": "Extended claims are outside the scope of this independent question. Not applicable does not mean that those extended effects are absent or that external full text has been read.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Direct dose comparisons, follow-up after discontinuation, and prespecified subgroup/interaction data needed when making such extended claims" }, { "item_id": "N37", "question_type": "Extension to clinical events", "question": "Does the claim also encompass prevention of falls, hospitalization, and death, and improvement in quality of life?", "needed": "Event definitions, observation windows, comparison denominators, and direct estimation data required when making claims about those events", "role": "Supplementary; required for extension to clinical events", "role_reason": "This is needed to prevent a functional-measurement question from automatically being extended to prevention of separate events.", "application_exception": "A mortality trial is not uniformly required for a question about change in usual speed itself. If the claim is extended, separate direct-evidence conditions are fixed.", "criterion": "Direct evidence on other clinical events and quality of life is addressed separately from the usual-speed question.", "basis": "M03 §3.2.4; internally designed boundaries for extensions / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "If event prevention becomes a new question, a design with definitions, follow-up, denominators, and comparisons for those events is reviewed separately.", "current_reports": [], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "The original question concerns usual walking function itself. Prevention of falls, hospitalization, and death, and improvement in quality of life are not adjudicated together with it.", "condition_status": "Not applicable", "status_reason": "Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome.", "missingness": "Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome.", "uncertainty": "Separate clinical events are outside the fixed question. This boundary of non-applicability does not imply an absence of effects on those events, nor does it remove the necessary conditions for the current speed outcome.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Event definitions, observation windows, comparison denominators, and direct estimation data required when making claims about those events" }, { "item_id": "N38", "question_type": "Search scope and 0", "question": "Do 0 direct results and no_human_study mean that all human NR research amounts to 0?", "needed": "The original search reference date, selection records, and explicit scope within which directly eligible results were checked", "role": "Required", "role_reason": "This is needed so that the different meanings of the numeric value 0 and the historical boolean do not produce a false declaration of absence.", "application_exception": "The original log files and ZIP were not opened this time, so the search as of the reference date is neither rerun nor presented as a current, up-to-date comprehensive review.", "criterion": "The scope of the original 0 and the compatibility boolean is preserved, without extending it to 0 effect, 0 human studies, or worldwide absence.", "basis": "M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design / M03 §3.1, §3.2.1–3.2.4 principles for clarifying the question; detailed separation rules are internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Future evidence updates retain the same boundaries, search dates, and eligibility records, and distinguish new results from existing plans and other outcomes.", "current_reports": [], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "In the logged search as of 2026-09-15, no directly eligible result for the fixed question was verified; that is the meaning of the original 0. human_NR_trials_exist=true and no_human_study=true coexist; the latter has the narrow meaning of a gate for calculator compatibility.", "condition_status": "Verified", "status_reason": "The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment.", "missingness": "The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment.", "uncertainty": "The original grade_semantics specifies the scope. The original ? and null score are preserved, without carrying them over as this table's verification status, an efficacy probability, or a new judgment.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The original search reference date, selection records, and explicit scope within which directly eligible results were checked" }, { "item_id": "N39", "question_type": "Reading of materials", "question": "Are the currently preserved archived summaries distinguished from external access and full-text reading at that earlier time?", "needed": "Each report's actual material type, original address, current access-not-attempted/unread status, historical access_level/date, and original location", "role": "Required", "role_reason": "This is needed to avoid confusing links, historical access records, and local summaries with current full-text reading.", "application_exception": "Current access that was not attempted is not labeled as failed. A historical description of full-text access is not copied to another material type for the same article.", "criterion": "Reading the local summaries now is not presented as current reading of external abstracts, full texts, or registrations; historical access levels are kept separate for each report.", "basis": "M04 §4.5–4.6 principles for data collection/selection; the separation of access from reading and the hyperlink contract are internally designed / M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "When materials are acquired, their original locations, access events, dates, and material types are recorded by report, and original summaries are distinguished from directly obtained full texts. This is a method for reviewing materials, separate from a clinical trial proposal.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S08", "S09", "S10", "S11", "S12", "S13", "S14", "S15", "S17", "S18" ], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "This time, the entire KO/EN text, structure, bibliography, and history of the preserved archived summaries, identical to the current source, were read. Report-specific access records dated 2026-09-15 for official indexes, application shells, abstracts, figure legends, HTML, and correction metadata are historical records. External materials have not been accessed or read this time; access has not been attempted.", "condition_status": "Verified", "status_reason": "The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now.", "missingness": "The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now.", "uncertainty": "The scope of the current summary reading and the attribution of the historical access descriptions were checked. The existence of publisher, PMC, and official links is distinguished from having read the full text now.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "Each report's actual material type, original address, current access-not-attempted/unread status, historical access_level/date, and original location" }, { "item_id": "N40", "question_type": "Preservation of history", "question": "Were the original ?, null values, axes, calculations, and publication metadata preserved without a new judgment?", "needed": "The exact original values for the original judgment, unscored axes, historical arithmetic, document quality, and manuscript publication/deployment metadata", "role": "Required", "role_reason": "This is needed to prevent the status of the table conversion from being misread as an existing grade, a calculated value, or a public publication event.", "application_exception": "Values, grades, and reading scopes from other current judgments are not carried over to this table. The original ? is not used as a simple substitute label for unread materials.", "criterion": "Native typed values and historical records are preserved in their original form, without elevating them to new efficacy or safety grades, check scores, or completed publication.", "basis": "M04 §4.5, §4.6.3; limits on the current data transformation follow the user's scope and internal design / M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed", "condition_origin": "Chamgap internal design and adaptation for the individual model; not a formal RoB/GRADE assessment, preregistration, or independent clinical certification", "proposed_research": "Future updates preserve the source bytes before and after changes and the reasons for changes, and distinguish changes in conditions, additions of materials, and new publication events.", "current_reports": [], "existence": "The relevant locations in the retained summary currently held were actually read. External materials were not attempted or read.", "acquired_read": "The native summaries and values in the retained manuscript were read. External papers, official documents, and registrations remain unread in the current review.", "observation": "Record from the time the preservation table was prepared: The original grade ?, null score, B/P, unscored axes, compatibility boolean, 4 historical arithmetic calculations, document self-review, and publication reference date are preserved. In that record, the original deployed_at was null, and the map current at that time was also not publicly deployed.", "condition_status": "Verified", "status_reason": "Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time.", "missingness": "Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time.", "uncertainty": "Preservation of the original values is neither a new efficacy judgment nor document-quality certification. The preserved arithmetic was performed at that earlier time; no new clinical calculations were performed this time.", "review_date": "2026-10-05", "reading_status": "Original source unread · Retained summary read", "additional_material": "The exact original values for the original judgment, unscored axes, historical arithmetic, document quality, and manuscript publication/deployment metadata" } ], "reports": [ { "report_id": "S01", "title": "NADage investigators' web description of the plan", "url": "https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/dementia---clinical-studies/the-nadage-study/", "report_type": "Full text of a web document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F01", "independent_replication": "This report is linked to family F01. The number of independent replications for this question is unverified.", "observed_result": "This describes the planned population, 2,000 mg/day, 52 weeks, and the 6-minute walk/sensors. It is not an actual result for the target usual speed.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a web document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical public description of the plan. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S01-M1", "url": "https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/dementia---clinical-studies/the-nadage-study/", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.helse-bergen.no/en/neuro-sysmed-english/clinical-studies-at-neuro-sysmed/dementia---clinical-studies/the-nadage-study/" } ] }, { "report_id": "S02", "title": "NADage official registry index/application shell", "url": "https://clinicaltrials.gov/study/NCT06208527", "report_type": "Full registry document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F01", "independent_replication": "This report is linked to family F01. The number of independent replications for this question is unverified.", "observed_result": "Only the age/Fried criteria and placebo design from the official index are recorded. The full registration, its history, and posted results were not acquired at that time.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full registry document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S02-M1", "url": "https://clinicaltrials.gov/study/NCT06208527", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT06208527" } ] }, { "report_id": "S03", "title": "NR-VETS official registry index", "url": "https://clinicaltrials.gov/study/NCT04691986", "report_type": "Full registry document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F02", "independent_replication": "This report is linked to family F02. The number of independent replications for this question is unverified.", "observed_result": "This is a limited index of the official title and walking description. The full hierarchy, latest status, and target results are unverified.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full registry document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S03-M1", "url": "https://clinicaltrials.gov/study/NCT04691986", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT04691986" } ] }, { "report_id": "S04", "title": "NR-VETS institutional recruitment index", "url": "https://www.kumc.edu/research/landon-center-on-aging/research/information-for-research-volunteers/explore-study-opportunities.html", "report_type": "Full text of a web document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F02", "independent_replication": "This report is linked to family F02. The number of independent replications for this question is unverified.", "observed_result": "The population in the institutional index has Fried<3. It does not match the target frailty criterion, and the complete current materials are unverified.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a web document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical official index, body text not acquired. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S04-M1", "url": "https://www.kumc.edu/research/landon-center-on-aging/research/information-for-research-volunteers/explore-study-opportunities.html", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.kumc.edu/research/landon-center-on-aging/research/information-for-research-volunteers/explore-study-opportunities.html" } ] }, { "report_id": "S05", "title": "Orr MCI abstract, bibliography, and figure legends", "url": "https://pubmed.ncbi.nlm.nih.gov/37994989/", "report_type": "Article abstract and bibliography", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F03", "independent_replication": "This report is linked to family F03. The number of independent replications for this question is unverified.", "observed_result": "These are within-group p-values for walking in MCI. The 20 completers are not the analysis n for the target usual speed, nor is this a between-group estimate in m/s.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Article abstract and bibliography", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical abstract, bibliography, and figure legends. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S05-M1", "url": "https://pubmed.ncbi.nlm.nih.gov/37994989/", "bibliographic_url": null }, { "material_type": "Full text of a clinical research article", "public_status": "Direct full-text URL not acquired; bibliographic lead available", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "No direct URL for this clinical article's full text has been acquired, and no historical record of accessing its full text is available. The DOI is a bibliographic lead. This time, external full-text access was not attempted, and the full text was neither acquired nor read.", "material_id": "S05-M2", "url": null, "bibliographic_url": "https://doi.org/10.1007/s11357-023-00999-9" } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/37994989/" } ] }, { "report_id": "S08", "title": "Martens crossover article in healthy participants", "url": "https://www.nature.com/articles/s41467-018-03421-7", "report_type": "Full text of a clinical research article", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F04", "independent_replication": "This report is linked to family F04. The number of independent replications for this question is unverified.", "observed_result": "The study reported no overall improvement in motor function in healthy participants. The supplementary figures and usual-speed values were not extracted, and this finding is not transferred as refutation of the target effect in frailty.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a clinical research article", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S08-M1", "url": "https://www.nature.com/articles/s41467-018-03421-7", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.nature.com/articles/s41467-018-03421-7" } ] }, { "report_id": "S09", "title": "NICE PAD article", "url": "https://www.nature.com/articles/s41467-024-49092-5", "report_type": "Full text of a clinical research article", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F05", "independent_replication": "This report is linked to family F05. The number of independent replications for this question is unverified.", "observed_result": "The 6-month between-group 6MWD result in PAD of +17.6 m, one-sided 90% CI [+1.77,+∞) m, p=0.08 is a positive adjacent finding. It is not a result for the target usual speed in m/s.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a clinical research article", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S09-M1", "url": "https://www.nature.com/articles/s41467-024-49092-5", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.nature.com/articles/s41467-024-49092-5" } ] }, { "report_id": "S10", "title": "NICE publisher correction", "url": "https://www.nature.com/articles/s41467-024-51289-7", "report_type": "Full text of a correction", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "F05", "independent_replication": "This report is linked to family F05. The number of independent replications for this question is unverified.", "observed_result": "Only the existence and identifier of the correction were verified at that time. The content of the correction and its impact on the effect are unverified.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a correction", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical bibliographic verification, failed access to the body text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S10-M1", "url": "https://www.nature.com/articles/s41467-024-51289-7", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.nature.com/articles/s41467-024-51289-7" } ] }, { "report_id": "S11", "title": "EFSA 2019 NR chloride safety assessment", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/5775", "report_type": "Full text of an official web document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "REG-EFSA-2019", "independent_replication": "This report is linked to family REG-EFSA-2019. The number of independent replications for this question is unverified.", "observed_result": "This assesses use of a specified substance in healthy people. It does not guarantee 52-week safety at a high dose in frail participants or efficacy for walking.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official web document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S11-M1", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/5775", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/5775" } ] }, { "report_id": "S12", "title": "EFSA 2021 assessment of extended uses of NR chloride", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/6843", "report_type": "Full text of an official web document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "REG-EFSA-2021", "independent_replication": "This report is linked to family REG-EFSA-2021. The number of independent replications for this question is unverified.", "observed_result": "This is an official opinion for specified conditions of use. Those NR chloride conditions are not extrapolated to long-term safety at the target high dose.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of an official web document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML full text. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S12-M1", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/6843", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/6843" } ] }, { "report_id": "S13", "title": "Identification of an article on other NAD precursors", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8485915/", "report_type": "Full text of a clinical research article", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "ADJ-CONNELL", "independent_replication": "This report is linked to family ADJ-CONNELL. The number of independent replications for this question is unverified.", "observed_result": "This is identity screening for tryptophan, nicotinic acid, and NAM. These are not NR, and no numbers were newly extracted or reassessed.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a clinical research article", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical bibliographic index of the original article. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S13-M1", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8485915/", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8485915/" } ] }, { "report_id": "S14", "title": "Identification of an NMN article in healthy older men", "url": "https://www.nature.com/articles/s41514-022-00084-z", "report_type": "Full text of a clinical research article", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "ADJ-IGARASHI", "independent_replication": "This report is linked to family ADJ-IGARASHI. The number of independent replications for this question is unverified.", "observed_result": "NMN is not NR. Positive walking data are not transferred to the target molecule.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a clinical research article", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML title-and-abstract screening. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S14-M1", "url": "https://www.nature.com/articles/s41514-022-00084-z", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.nature.com/articles/s41514-022-00084-z" } ] }, { "report_id": "S15", "title": "Publisher abstract on NR+exercise in hypertension", "url": "https://link.springer.com/article/10.1007/s11357-025-01815-2", "report_type": "Article abstract and bibliography", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "ADJ-LIN", "independent_replication": "This report is linked to family ADJ-LIN. The number of independent replications for this question is unverified.", "observed_result": "This is screening material on a combined intervention involving exercise in hypertension. It is not a direct replication for usual speed in frailty.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Article abstract and bibliography", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical publisher abstract and later sections. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S15-M1", "url": "https://link.springer.com/article/10.1007/s11357-025-01815-2", "bibliographic_url": null }, { "material_type": "Full text of a clinical research article", "public_status": "Direct full-text URL not acquired; bibliographic lead available", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "No direct URL for this clinical article's full text has been acquired, and no historical record of accessing its full text is available. The DOI is a bibliographic lead. This time, external full-text access was not attempted, and the full text was neither acquired nor read.", "material_id": "S15-M2", "url": null, "bibliographic_url": "https://doi.org/10.1007/s11357-025-01815-2" } ], "links": [ { "label": "Source", "url": "https://link.springer.com/article/10.1007/s11357-025-01815-2" } ] }, { "report_id": "S17", "title": "NICE-FIT official registry title", "url": "https://clinicaltrials.gov/study/NCT06465602", "report_type": "Full registry document", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "ADJ-NICE-FIT", "independent_replication": "This report is linked to family ADJ-NICE-FIT. The number of independent replications for this question is unverified.", "observed_result": "The substance in the title is nicotinamide. NR identity, product, and results are unverified, so this is not used as direct NR evidence.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full registry document", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical official index title. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S17-M1", "url": "https://clinicaltrials.gov/study/NCT06465602", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://clinicaltrials.gov/study/NCT06465602" } ] }, { "report_id": "S18", "title": "Identification of an article on a combination intervention and cognition in older dogs", "url": "https://www.nature.com/articles/s41598-024-63031-w", "report_type": "Full text of a nonhuman research article", "existence": "This is a reference from the archived bibliography and historical records; the current external response has not been checked.", "acquired_read": "The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external source materials have not been read this time.", "study_family": "ADJ-DOG", "independent_replication": "This report is linked to family ADJ-DOG. The number of independent replications for this question is unverified.", "observed_result": "The species, intervention, and endpoint do not match: older dogs, a combination product, and owner assessments of cognition. Effect estimates in dogs were not used.", "result_level": "This is content recorded in the archived manuscript. It is not the result of a new comparison against external source materials this time.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Full text of a nonhuman research article", "public_status": "Currently unverified", "access_status": "Not attempted this time", "acquired": false, "actually_read": "Unread", "as_of": "2026-11-01", "qualification": "Historical access date for this material: 2026-09-15; recorded level: historical HTML title-and-abstract screening. This time, only the archived summaries were read; external access was not attempted, and the external materials were neither acquired nor read.", "material_id": "S18-M1", "url": "https://www.nature.com/articles/s41598-024-63031-w", "bibliographic_url": null } ], "links": [ { "label": "Source", "url": "https://www.nature.com/articles/s41598-024-63031-w" } ] } ], "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": "Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full." }, { "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 exclude a study solely because its results are unreported.", "review_level": "Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full." }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, deviations, missingness, measurement, and selective reporting.", "review_level": "Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full." }, { "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. Precision is not determined by sample size alone.", "review_level": "Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full." }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Questions about harms may require designs, populations, and follow-up that differ from those for efficacy. Case reports do not establish incidence rates.", "review_level": "Reuse of actual original-byte/SHA copies of the methodological files preserved from the 1585 pilot. The full methodological texts were not newly read this time, nor were the official methods implemented in full." } ], "status_dictionary": { "Verified": "Verification of the stated question and boundaries in the preserved materials; not confirmation of efficacy or safety.", "Partly verified": "Only some information has been verified; the full set of necessary conditions remains unverified.", "Unverified": "Direct materials, methods, and results within the scope of the current input are unverified. This does not mean that studies are absent or that the intervention is ineffective.", "Not met": "The actual population, endpoint, or exposure in the materials does not match the fixed question. This is not a judgment of efficacy failure.", "Not applicable": "An extension condition outside the narrow question. This status must not be used in place of recording that a full text has not been read." }, "study_overlap": { "state": "The 5 families of plans and adjacent trials and the 15 reports do not represent a count of direct usual-speed trials, an effect of 0, or a count of independent replications. Despite the S05–S07 range notation, individual S06/S07 entries are absent from the current citation list. The numbers of unique eligible trials, participants, and independent replications are unverified.", "unique_trial_count": null, "unique_participant_count": null, "reason": "The 5 families of plans and adjacent trials and the 15 reports do not represent a count of direct usual-speed trials, an effect of 0, or a count of independent replications. Despite the S05–S07 range notation, individual S06/S07 entries are absent from the current citation list. The numbers of unique eligible trials, participants, and independent replications are unverified." }, "history": [ { "date": "2026-11-01", "kind": "Separation of public display and data", "view_version": "1.0", "change": "Public-facing display and data were created from the existing 40 items. No new clinical searches, changes in verification status, or scoring were performed." } ], "language": "en", "translation_date": "2026-11-01" }