Two-year caloric restriction × slower DunedinPACE: a post hoc DNA-surrogate evidence checklist

Required evidence, verification status and materials actually read
Item	AVerification status	BReading scope	CReview item	DCurrent findings	EWhy unverified	FRequired materials and conditions	GFurther research
1	Partly verified	Full text not readStored summary read	N01 · Comparative efficacyAre the original DunedinPACE subclaim assessment and the parent pace-of-aging context kept separate?Required	The subclaim concerns 'Slower DunedinPACE', with original grade C and a note of a roughly 2~3% slowing signal. The parent surrogate assessment is C, 54 points and Unknown safety. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment.	Separate records of the original claim, grade, note and parent values	If additional original material is provided, connect the selected measure separately from the parent context.
2	Partly verified	Full text not readStored summary read	N02 · Comparative efficacyWhat population and applicability limits concern healthy non-obese adults?Required	The original population was healthy non-obese adults, and CALERIE took place at three US sites. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations.	Age, baseline condition, obesity status, eligibility and population-specific denominators	Obtain original eligibility, baseline characteristics and recruitment denominators.
3	Partly verified	Full text not readStored summary read	N03 · Comparative efficacyAre the target caloric restriction and achieved average exposure distinguished?Required	The historical study target was 25% restriction, whereas the original account reports average achieved restriction of about 12%. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read.	Study records of the original target, achieved exposure, measurement, adherence and duration	Obtain original exposure measurements, adherence, support and change records.
4	Partly verified	Full text not readStored summary read	N04 · Comparative efficacyCan the intervention and control diets, support and concurrent exposures over two years be verified?Required	The original intervention was two-year caloric restriction, and the positive finding is recorded as a randomized comparison with a control group. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed.	Actual intervention and control diets, support, contact and concurrent management	Connect protocol records of the control, support, achieved exposure and concurrent management.
5	Partly verified	Full text not readStored summary read	N05 · Comparative efficacyDo 220 randomized participants, 2:1 allocation and the 197-person DNA sample share a denominator?Required	CALERIE randomized 220 participants in a 2:1 ratio. DNA data were analyzed for 197 participants with baseline and at least one follow-up sample. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months.	Randomization, sample acquisition, measure-specific analyses and time-specific denominators	Obtain original tables tracing allocation, DNA samples and analyses by time and measure.
6	Partly verified	Full text not readStored summary read	N06 · Comparative efficacyDo gaps remain concerning DNA sample selection, follow-up, missingness and the effect of interest?Required	The original DNA analysis requirement of baseline and at least one follow-up sample is preserved. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated.	Sample selection, missingness by group, analysis populations, sensitivity analyses and original models	Obtain original sample-selection, group-specific missingness, analysis-population and sensitivity plans.
7	Partly verified	Full text not readStored summary read	N07 · Comparative efficacyIs DunedinPACE a pace measure distinct from clinical events?Required	The original account describes DunedinPACE as a DNA-methylation measure of the pace of aging and a surrogate rather than a clinical event. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read.	DNA measure definitions, measurement units, validation and measurement procedures	Obtain original measure definitions, validation, measurement, units and clinical-linkage material.
8	Unverified	Full text not readStored summary read	N08 · Comparative efficacyAre details of DNA measurement, batches, normalization and measure calculation available?Required	The post hoc DNA-methylation design and analyst blinding are preserved. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated.	Original methods for samples, DNA measurement, batches, normalization and algorithms	Obtain original laboratory, measure-calculation and quality-processing methods.
9	Partly verified	Full text not readStored summary read	N09 · Comparative efficacyAre the original 12-month DunedinPACE effect and CI preserved?Required	The original account records the 12-month effect as d=−0.29 (95% CI −0.45 to −0.13). R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read.	Original effects, units, CIs, models and denominators by time	Obtain the original 12-month model, adjustments, denominators, effect and CI.
10	Partly verified	Full text not readStored summary read	N10 · Comparative efficacyIs the 24-month DunedinPACE effect and interval preserved as a separate time-specific value?Required	The original wording d=−0.25 (−0.41 to −0.09) at 24 months is preserved. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated.	Original effects, original intervals, models and denominators by time	Obtain the original 24-month effect, interval level, model and time-specific denominators.
11	Partly verified	Full text not readStored summary read	N11 · Comparative efficacyWhat is the scope of P<0.003 and the roughly 2~3% wording?Required	The original rationale presents the DunedinPACE values at 12 and 24 months together with P<0.003. The reader answer and note describe roughly 2~3% slowing. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life.	Links between time-specific tests, effect transformations and original estimates	Obtain the original definitions and models for time-specific tests and percentage wording.
12	Partly verified	Full text not readStored summary read	N12 · Comparative efficacyAre the null PC PhenoAge and PC GrimAge findings preserved together?Required	The original account describes the other two measures as null, with d −0.04 to 0.05 and P>0.15. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks.	Original effects, intervals and tests by distinct measure and time	Obtain effects, CIs, P values and denominators separately for each PC measure and time.
13	Partly verified	Full text not readStored summary read	N13 · Comparative efficacyDo the pace measure and the two PC clocks use the same units and address the same question?Required	The original account distinguishes a result in which only one of three DNA-methylation measures changed. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read.	Definitions, reference standards, units and interpretation limits for each measure	Obtain original definitions, validation, units and applicability material for each measure.
14	Partly verified	Full text not readStored summary read	N14 · Comparative efficacyAre the post hoc analysis and the parent's prespecified clinical primary endpoint distinguished?Required	The paper explicitly identifies the analysis as post hoc. The original account states that the DNA outcomes were not the parent trial's prespecified clinical primary endpoint. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized.	Original registration, protocol, SAP, analysis timing and outcome hierarchy	Obtain original registration, protocol and SAP, and records of post hoc analysis selection and changes.
15	Partly verified	Full text not readStored summary read	N15 · Comparative efficacyAre the split findings across three measures and the multiple-outcome analysis plan preserved?Required	The original account assesses only one of three measures as positive and the key measures as split; the parent split-key-measures flag remains true. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read.	Original plans for three measures, time points, models, tests and multiplicity handling	Obtain the DNA analysis's original outcome list, time points, tests, adjustments and selective-reporting plan.
16	Partly verified	Full text not readStored summary read	N16 · Comparative efficacyIs the absence of a clinical minimum-effect threshold and prespecified success boundary preserved?Required	The original account records no clinical minimum-effect threshold or prespecified success boundary and describes the effects as small. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects.	Clinical validation, minimum-effect thresholds and plans for each measure	Connect clinical validation, prespecified thresholds and plans for each measure if provided.
17	Partly verified	Full text not readStored summary read	N17 · Comparative efficacyWhat is the original scope of allocation and analyst blinding?Required	The Korean account says that analysts did not know allocation; the English account specifies 'laboratory analysts blinded'. The parent's 2:1 randomized design is also preserved. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read.	Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures	Obtain original allocation, laboratory and measure-analysis methods and blinding roles.
18	Unverified	Full text not readStored summary read	N18 · Comparative efficacyIs the relationship between achieved restriction, adherence, weight changes and measure effects directly verified?Required	The 25% target and average achieved restriction of about 12% are preserved as historical study conditions. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms.	Original achieved exposure, adherence, concurrent changes and effects of interest	Obtain achieved exposure, adherence, concurrent changes and prespecified mediation or effect-of-interest material.
19	Unverified	Full text not readStored summary read	N19 · Comparative efficacyDo gaps remain concerning persistence after 12 or 24 months, mechanisms and other aging measures?Required	The original DNA effects are presented at 12 and 24 months, and the intervention lasted two years. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in.	Follow-up measures, duration, denominators, original effects and direct mechanism evidence	Obtain direct post-intervention follow-up and original measurements, denominators and effects separately by measure.
20	Partly verified	Full text not readStored summary read	N20 · Comparative efficacyHas the result been kept separate from disease, disability, death, lifespan and independent-living outcomes?Required	The original account explicitly states that reduced disease, disability or death was not measured and longer healthy life was not answered. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living.	Direct clinical endpoints, adequate follow-up, events, denominators and effects	Direct definitions, long-term follow-up, denominators and effect data are needed for each clinical outcome.
21	Partly verified	Full text not readStored summary read	N21 · Comparative efficacyAre the two sibling sheets, two time points and one post hoc report kept from being independently summed?Required	Both sheets share the same CALERIE post hoc report and the 220-person and 197-person context. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded.	Relationships among the parent trial, post hoc report, same participants, measures and time points	Link additional reports through original trial identifiers while retaining relationships to the same population.
22	Partly verified	Full text not readStored summary read	N22 · Comparative efficacyAre funding and DunedinPACE invention and commercial-licensing interests distinguished?Required	Support from NIA, American Brain Foundation, CIHR and others, authorship by inventors D.L. Corcoran and D.W. Belsky, and commercial licensing are preserved. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read.	Funding, authors, invention, licensing, provision and analysis roles	Obtain original funding, licensing, affiliations, product or service provision, analysis and manuscript roles separately.
23	Partly verified	Full text not readStored summary read	N23 · Supplementary harm evidenceDoes absent safety reporting establish that the parent trial had no harms?Required	This post hoc analysis did not report safety as an endpoint, and the parent's safety assessment is Unknown. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE.	Harm plans, events by group and exposure denominators for this analysis and the parent trial	Obtain the parent trial's original harm plans, events by group, exposure, discontinuation and denominators separately.
24	Unverified	Full text not readStored summary read	N24 · Supplementary harm evidenceDo gaps remain concerning long-term or rare harms under two-year achieved exposure?Required	The original safety account states that this analysis cannot determine harms of long-term caloric restriction. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented.	Direct harm data by achieved exposure, discontinuation, severity and duration	Obtain group-specific harms, discontinuation, rare events and long-term data from the parent trial and follow-up reports.
25	Unverified	Full text not readStored summary read	N25 · Supplementary harm evidenceAre harm replication, applicability to other populations or exposures, and dietary instructions distinguished?Required	The current population is healthy non-obese adults, and the historical exposure is a two-year study with differing target and achieved average restriction. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created.	Direct effects, harms, exposures and same-population relationships by population	Connect direct comparisons and harm evidence for new populations or exposures separately.
26	Partly verified	Full text not readStored summary read	N26 · Comparative efficacyAre the stored summary, PubMed link and registration identifier distinguished from materials actually read?Required	The whole parent summary was read for production, and the original PubMed link and NCT00427193 identifier were connected. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested.	Separate access records for the summary, abstract, full text, registration, protocol and SAP	Connect additional provided material with its individual access status.
27	Partly verified	Full text not readStored summary read	N27 · Comparative efficacyAre original dates, Korean and English text, empty values, subclaim and parent values, and review status preserved?Supplementary	The 2026-08-26 reference date, empty correction and deliberation values, Korean and English text, C54, original axes and subclaim C are preserved. Original pending and production-eligible markers are historical; content review at that time remained incomplete. R01	Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The missing subclaim score and unrecorded precision are not filled in. Original model, content and scope review activation and completion remain false; added assessment units are 0 and the final independent count is unrecorded.	Distinction among the complete original, selected assessment record, history and current production status	Proposal: Reflect additional materials and decisions through preservation of original wording and separate events.

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27 itemsWhat the statuses mean

Assessment scope

Stored-material review date: Not recorded
Original evidence cut-off: 2026-08-26
Scope actually checked: Existing review summaries and stored records of methodological application. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the stored materials were checked, not the date of a new search of the clinical literature.
Population: Healthy non-obese adults in CALERIE; three US sites; detailed eligibility not read
Ingredient, formulation and route: Historical two-year caloric-restriction study intervention; not personal calorie, diet or weight-loss instructions
Dose: Original target of 25% and achieved average of about 12% preserved separately; individual and time-specific exposure details not read
Comparator: Parent randomized control group; specific control diet, support and concurrent management not read
Measured outcome: Selected slower-DunedinPACE question; the two PC measures and clinical outcomes kept separate
Duration: Two-year study intervention; details of DunedinPACE at 12 and 24 months and time-specific PC outcomes unverified; post-intervention follow-up unverified
Questions outside this scope: Recasting a DNA measure as clinical rejuvenation, aging in general, disease, disability, death, lifespan or independent living; Treating target exposure and the achieved average as identical; Summing time points, measures, the 197-person DNA denominator or sibling sheets as new independent evidence; Personal calorie, dietary, weight-loss or treatment instructions

Evidence and sources

The links below lead to the sources. A link alone does not mean the original source was read or its latest publication status verified.

R01 · Waziry R, Ryan CP, Corcoran DL, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nat Aging. 2023;3:248-257. PMID: 37118425.

PubMed

Material type: Post hoc DNA-analysis report from the parent randomized trial
Materials actually read: Summary read; external materials not read
Findings recorded in the stored summary: Only DunedinPACE changed: d=−0.29 at 12 months and d=−0.25 at 24 months; the other two clocks were null
Record level: Stored evidence-list and narrative summaries; not direct reading of the original paper or registration
Study overlap and independent replication: Post hoc DNA analysis of the CALERIE parent randomized trial; the two subclaim sheets, measures and time points are shared, rather than separate new trials. Family IDs connect relationships and do not certify unique trial counts; reports, time points, measures, sibling sheets and the same participants are not newly summed as independent evidence.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
local_summary	Original source link preserved	Summary read	Summary read	Preserved parent verdict summary
abstract	Original source link preserved	Not read	Not read	External material unread; a URL does not mean acquisition, reading or completed review
fulltext	No separate URL in the original material	Not read	Not read	External material unread; a URL does not mean acquisition, reading or completed review
registration	No separate URL in the original material	Not read	Not read	External material unread; a URL does not mean acquisition, reading or completed review
protocol_sap	No separate URL in the original material	Not read	Not read	External material unread; a URL does not mean acquisition, reading or completed review

Report counts versus independent study counts

Post hoc DNA analysis of the CALERIE parent randomized trial; the two subclaim sheets, measures and time points are shared, rather than separate new trials. Family IDs connect relationships and do not certify unique trial counts; reports, time points, measures, sibling sheets and the same participants are not newly summed as independent evidence.

Review criteria

Version 1.0 · Criteria record date 2026-10-06. These are Chamgap's own application conditions, informed by the referenced methods. They do not constitute official assessment-tool certification or a new efficacy score.

N01 · Are the original DunedinPACE subclaim assessment and the parent pace-of-aging context kept separate?

Required materials and conditions: Separate records of the original claim, grade, note and parent values
Conditions for verification: Separate records of the original claim, grade, note and parent values
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N02 · What population and applicability limits concern healthy non-obese adults?

Required materials and conditions: Age, baseline condition, obesity status, eligibility and population-specific denominators
Conditions for verification: Age, baseline condition, obesity status, eligibility and population-specific denominators
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N03 · Are the target caloric restriction and achieved average exposure distinguished?

Required materials and conditions: Study records of the original target, achieved exposure, measurement, adherence and duration
Conditions for verification: Study records of the original target, achieved exposure, measurement, adherence and duration
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N04 · Can the intervention and control diets, support and concurrent exposures over two years be verified?

Required materials and conditions: Actual intervention and control diets, support, contact and concurrent management
Conditions for verification: Actual intervention and control diets, support, contact and concurrent management
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N05 · Do 220 randomized participants, 2:1 allocation and the 197-person DNA sample share a denominator?

Required materials and conditions: Randomization, sample acquisition, measure-specific analyses and time-specific denominators
Conditions for verification: Randomization, sample acquisition, measure-specific analyses and time-specific denominators
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N06 · Do gaps remain concerning DNA sample selection, follow-up, missingness and the effect of interest?

Required materials and conditions: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models
Conditions for verification: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N07 · Is DunedinPACE a pace measure distinct from clinical events?

Required materials and conditions: DNA measure definitions, measurement units, validation and measurement procedures
Conditions for verification: DNA measure definitions, measurement units, validation and measurement procedures
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N08 · Are details of DNA measurement, batches, normalization and measure calculation available?

Required materials and conditions: Original methods for samples, DNA measurement, batches, normalization and algorithms
Conditions for verification: Original methods for samples, DNA measurement, batches, normalization and algorithms
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N09 · Are the original 12-month DunedinPACE effect and CI preserved?

Required materials and conditions: Original effects, units, CIs, models and denominators by time
Conditions for verification: Original effects, units, CIs, models and denominators by time
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N10 · Is the 24-month DunedinPACE effect and interval preserved as a separate time-specific value?

Required materials and conditions: Original effects, original intervals, models and denominators by time
Conditions for verification: Original effects, original intervals, models and denominators by time
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N11 · What is the scope of P<0.003 and the roughly 2~3% wording?

Required materials and conditions: Links between time-specific tests, effect transformations and original estimates
Conditions for verification: Links between time-specific tests, effect transformations and original estimates
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N12 · Are the null PC PhenoAge and PC GrimAge findings preserved together?

Required materials and conditions: Original effects, intervals and tests by distinct measure and time
Conditions for verification: Original effects, intervals and tests by distinct measure and time
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N13 · Do the pace measure and the two PC clocks use the same units and address the same question?

Required materials and conditions: Definitions, reference standards, units and interpretation limits for each measure
Conditions for verification: Definitions, reference standards, units and interpretation limits for each measure
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N14 · Are the post hoc analysis and the parent's prespecified clinical primary endpoint distinguished?

Required materials and conditions: Original registration, protocol, SAP, analysis timing and outcome hierarchy
Conditions for verification: Original registration, protocol, SAP, analysis timing and outcome hierarchy
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N15 · Are the split findings across three measures and the multiple-outcome analysis plan preserved?

Required materials and conditions: Original plans for three measures, time points, models, tests and multiplicity handling
Conditions for verification: Original plans for three measures, time points, models, tests and multiplicity handling
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N16 · Is the absence of a clinical minimum-effect threshold and prespecified success boundary preserved?

Required materials and conditions: Clinical validation, minimum-effect thresholds and plans for each measure
Conditions for verification: Clinical validation, minimum-effect thresholds and plans for each measure
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N17 · What is the original scope of allocation and analyst blinding?

Required materials and conditions: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures
Conditions for verification: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N18 · Is the relationship between achieved restriction, adherence, weight changes and measure effects directly verified?

Required materials and conditions: Original achieved exposure, adherence, concurrent changes and effects of interest
Conditions for verification: Original achieved exposure, adherence, concurrent changes and effects of interest
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N19 · Do gaps remain concerning persistence after 12 or 24 months, mechanisms and other aging measures?

Required materials and conditions: Follow-up measures, duration, denominators, original effects and direct mechanism evidence
Conditions for verification: Follow-up measures, duration, denominators, original effects and direct mechanism evidence
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N20 · Has the result been kept separate from disease, disability, death, lifespan and independent-living outcomes?

Required materials and conditions: Direct clinical endpoints, adequate follow-up, events, denominators and effects
Conditions for verification: Direct clinical endpoints, adequate follow-up, events, denominators and effects
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N21 · Are the two sibling sheets, two time points and one post hoc report kept from being independently summed?

Required materials and conditions: Relationships among the parent trial, post hoc report, same participants, measures and time points
Conditions for verification: Relationships among the parent trial, post hoc report, same participants, measures and time points
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N22 · Are funding and DunedinPACE invention and commercial-licensing interests distinguished?

Required materials and conditions: Funding, authors, invention, licensing, provision and analysis roles
Conditions for verification: Funding, authors, invention, licensing, provision and analysis roles
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N23 · Does absent safety reporting establish that the parent trial had no harms?

Required materials and conditions: Harm plans, events by group and exposure denominators for this analysis and the parent trial
Conditions for verification: Harm plans, events by group and exposure denominators for this analysis and the parent trial
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N24 · Do gaps remain concerning long-term or rare harms under two-year achieved exposure?

Required materials and conditions: Direct harm data by achieved exposure, discontinuation, severity and duration
Conditions for verification: Direct harm data by achieved exposure, discontinuation, severity and duration
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N25 · Are harm replication, applicability to other populations or exposures, and dietary instructions distinguished?

Required materials and conditions: Direct effects, harms, exposures and same-population relationships by population
Conditions for verification: Direct effects, harms, exposures and same-population relationships by population
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N26 · Are the stored summary, PubMed link and registration identifier distinguished from materials actually read?

Required materials and conditions: Separate access records for the summary, abstract, full text, registration, protocol and SAP
Conditions for verification: Separate access records for the summary, abstract, full text, registration, protocol and SAP
Requirement and applicability: Required
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

N27 · Are original dates, Korean and English text, empty values, subclaim and parent values, and review status preserved?

Required materials and conditions: Distinction among the complete original, selected assessment record, history and current production status
Conditions for verification: Distinction among the complete original, selected assessment record, history and current production status
Requirement and applicability: Supplementary
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Referenced methods: Slower DunedinPACE

Referenced methods and the sections actually reviewed

M03 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §3.1, §3.2.1–3.2.3, MECIR C5/C7/C13

Referenced principle: Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations in interventions.
Extent of review: Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed.

M04 · Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03

Official methodology · §4.5, §4.6.1–4.6.3, MECIR C42

Referenced principle: Distinguish studies from reports and link them; do not omit a study solely because results are unreported.
Extent of review: Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed.

M08 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §8.1–8.2.3, Table 8.2.a

Referenced principle: Define the outcome and effect of interest, then examine randomization, deviations, missing data, measurement and selective reporting.
Extent of review: Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed.

M15 · Cochrane Handbook 6.5 (2024), chapter updated 2023-08

Official methodology · §15.2.4, §15.3.1–15.3.3

Referenced principle: Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.
Extent of review: Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed.

M19 · Cochrane Handbook 6.5 (2024), chapter updated 2019-10

Official methodology · §19.1.2, §19.2.1–19.2.4

Referenced principle: Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence rates.
Extent of review: Preserved methodology connections were reused for preparation. No new review of methodological content, reassessment or external-link checks were performed.

What the statuses mean

Partly verified: Some information exists in the preserved review summary; detailed original materials remain unverified. This does not certify a passed review or clinical efficacy.
Unverified: Detailed materials for the selected condition could not be established within the stored scope; this does not mean zero effect, zero studies or safety
Review incomplete: Review of existing content incomplete
Met: Use only within the relevant conditions after existing content review; no automatic designation in this preparation
Not reported: Distinguish only within materials actually read; do not turn unread external materials into unreported findings
Inaccessible: Not applied during this preparation because actual access was not tested
Not applicable: Use with a reason for non-applicability based on an explicit question boundary
Conflicting data: Judge after actual material comparison; review was not performed during this preparation
Insufficient evidence for the conditions: Do not use as a clinical grade encompassing currently unread materials

Change history

2026-10-11 · Public page/material version 1.0

Public pages and materials were prepared from the existing 27 items. No new clinical search, verification-status change or scoring was performed.

The stored-material review date (Not recorded) and original evidence cut-off (2026-08-26) were retained unchanged.

Researcher downloads

These materials provide the same evidence, scope and verification status as this page.

View all item details

N01 · Are the original DunedinPACE subclaim assessment and the parent pace-of-aging context kept separate?

Current findings: The subclaim concerns 'Slower DunedinPACE', with original grade C and a note of a roughly 2~3% slowing signal. The parent surrogate assessment is C, 54 points and Unknown safety.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment.
Reason for missing information: The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment.
Required materials and conditions: Separate records of the original claim, grade, note and parent values
Materials to obtain first: The subclaim has no score, status or axes; parent values are not used to fill them. This is not a new clinical assessment.
Further research: If additional original material is provided, connect the selected measure separately from the parent context.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Separate records of the original claim, grade, note and parent values
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N02 · What population and applicability limits concern healthy non-obese adults?

Current findings: The original population was healthy non-obese adults, and CALERIE took place at three US sites.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations.
Reason for missing information: Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations.
Required materials and conditions: Age, baseline condition, obesity status, eligibility and population-specific denominators
Materials to obtain first: Detailed age, BMI, disease and eligibility criteria are absent from this summary. Findings are not automatically applied to aging or disease effects in other populations.
Further research: Obtain original eligibility, baseline characteristics and recruitment denominators.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Age, baseline condition, obesity status, eligibility and population-specific denominators
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N03 · Are the target caloric restriction and achieved average exposure distinguished?

Current findings: The historical study target was 25% restriction, whereas the original account reports average achieved restriction of about 12%.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read.
Reason for missing information: The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read.
Required materials and conditions: Study records of the original target, achieved exposure, measurement, adherence and duration
Materials to obtain first: The target and achieved exposure are not treated as identical or presented as personal dietary, calorie or weight-loss targets. Individual exposure, estimation and changes over time have not been read.
Further research: Obtain original exposure measurements, adherence, support and change records.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Study records of the original target, achieved exposure, measurement, adherence and duration
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N04 · Can the intervention and control diets, support and concurrent exposures over two years be verified?

Current findings: The original intervention was two-year caloric restriction, and the positive finding is recorded as a randomized comparison with a control group.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed.
Reason for missing information: Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed.
Required materials and conditions: Actual intervention and control diets, support, contact and concurrent management
Materials to obtain first: Specific control diets, contact, support and concurrent management are absent from this summary. Equivalent calorie, nutrient or attention conditions are not newly confirmed.
Further research: Connect protocol records of the control, support, achieved exposure and concurrent management.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Actual intervention and control diets, support, contact and concurrent management
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N05 · Do 220 randomized participants, 2:1 allocation and the 197-person DNA sample share a denominator?

Current findings: CALERIE randomized 220 participants in a 2:1 ratio. DNA data were analyzed for 197 participants with baseline and at least one follow-up sample.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months.
Reason for missing information: Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months.
Required materials and conditions: Randomization, sample acquisition, measure-specific analyses and time-specific denominators
Materials to obtain first: Group sizes are not newly calculated from the allocation ratio. The 197 participants are not assumed to be the denominator for every measure at both 12 and 24 months.
Further research: Obtain original tables tracing allocation, DNA samples and analyses by time and measure.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Randomization, sample acquisition, measure-specific analyses and time-specific denominators
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N06 · Do gaps remain concerning DNA sample selection, follow-up, missingness and the effect of interest?

Current findings: The original DNA analysis requirement of baseline and at least one follow-up sample is preserved.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated.
Reason for missing information: Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated.
Required materials and conditions: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models
Materials to obtain first: Reasons for DNA exclusions, missingness by time, ITT status and sample-selection effects have not been read. Attrition rates or missing counts are not newly calculated.
Further research: Obtain original sample-selection, group-specific missingness, analysis-population and sensitivity plans.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Sample selection, missingness by group, analysis populations, sensitivity analyses and original models
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N07 · Is DunedinPACE a pace measure distinct from clinical events?

Current findings: The original account describes DunedinPACE as a DNA-methylation measure of the pace of aging and a surrogate rather than a clinical event.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read.
Reason for missing information: The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read.
Required materials and conditions: DNA measure definitions, measurement units, validation and measurement procedures
Materials to obtain first: The result is not converted into clinical aging itself, reduced disease, rejuvenation or years of life. Details of the formula, units and clinical calibration have not been read.
Further research: Obtain original measure definitions, validation, measurement, units and clinical-linkage material.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: DNA measure definitions, measurement units, validation and measurement procedures
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N08 · Are details of DNA measurement, batches, normalization and measure calculation available?

Current findings: The post hoc DNA-methylation design and analyst blinding are preserved.
Verification status: Unverified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated.
Reason for missing information: Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated.
Required materials and conditions: Original methods for samples, DNA measurement, batches, normalization and algorithms
Materials to obtain first: Sample types, laboratory platforms, batches, normalization and algorithm details are not inferred, and measures are not newly calculated.
Further research: Obtain original laboratory, measure-calculation and quality-processing methods.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original methods for samples, DNA measurement, batches, normalization and algorithms
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N09 · Are the original 12-month DunedinPACE effect and CI preserved?

Current findings: The original account records the 12-month effect as d=−0.29 (95% CI −0.45 to −0.13).
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read.
Reason for missing information: The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read.
Required materials and conditions: Original effects, units, CIs, models and denominators by time
Materials to obtain first: The standardized effect d is not recalculated into years of aging, percentages or clinical-event effects. Time-specific group denominators and model details have not been read.
Further research: Obtain the original 12-month model, adjustments, denominators, effect and CI.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original effects, units, CIs, models and denominators by time
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N10 · Is the 24-month DunedinPACE effect and interval preserved as a separate time-specific value?

Current findings: The original wording d=−0.25 (−0.41 to −0.09) at 24 months is preserved.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated.
Reason for missing information: The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated.
Required materials and conditions: Original effects, original intervals, models and denominators by time
Materials to obtain first: The 12-month 95% label is not added to the 24-month interval without separate verification in the original paper. A mean of the two time points or a persistence rate is not calculated.
Further research: Obtain the original 24-month effect, interval level, model and time-specific denominators.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original effects, original intervals, models and denominators by time
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N11 · What is the scope of P<0.003 and the roughly 2~3% wording?

Current findings: The original rationale presents the DunedinPACE values at 12 and 24 months together with P<0.003. The reader answer and note describe roughly 2~3% slowing.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life.
Reason for missing information: The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life.
Required materials and conditions: Links between time-specific tests, effect transformations and original estimates
Materials to obtain first: The P threshold is not turned into separate exact values for each time point, and 2~3% is not newly calculated from d. It is not converted into a rate of longer healthy life.
Further research: Obtain the original definitions and models for time-specific tests and percentage wording.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Links between time-specific tests, effect transformations and original estimates
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N12 · Are the null PC PhenoAge and PC GrimAge findings preserved together?

Current findings: The original account describes the other two measures as null, with d −0.04 to 0.05 and P>0.15.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks.
Reason for missing information: The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks.
Required materials and conditions: Original effects, intervals and tests by distinct measure and time
Materials to obtain first: The range endpoints are not assigned separately to individual measures or time points. The finding is not extended to slowing of all DNA clocks.
Further research: Obtain effects, CIs, P values and denominators separately for each PC measure and time.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original effects, intervals and tests by distinct measure and time
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N13 · Do the pace measure and the two PC clocks use the same units and address the same question?

Current findings: The original account distinguishes a result in which only one of three DNA-methylation measures changed.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read.
Reason for missing information: The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read.
Required materials and conditions: Definitions, reference standards, units and interpretation limits for each measure
Materials to obtain first: The pace-measure effect is not copied as an effect or value for PC biological age. Exact differences in units and validation have not been read.
Further research: Obtain original definitions, validation, units and applicability material for each measure.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Definitions, reference standards, units and interpretation limits for each measure
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N14 · Are the post hoc analysis and the parent's prespecified clinical primary endpoint distinguished?

Current findings: The paper explicitly identifies the analysis as post hoc. The original account states that the DNA outcomes were not the parent trial's prespecified clinical primary endpoint.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized.
Reason for missing information: The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized.
Required materials and conditions: Original registration, protocol, SAP, analysis timing and outcome hierarchy
Materials to obtain first: The DNA analysis is not recast as a prespecified confirmatory primary analysis merely because its parent trial was randomized.
Further research: Obtain original registration, protocol and SAP, and records of post hoc analysis selection and changes.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original registration, protocol, SAP, analysis timing and outcome hierarchy
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N15 · Are the split findings across three measures and the multiple-outcome analysis plan preserved?

Current findings: The original account assesses only one of three measures as positive and the key measures as split; the parent split-key-measures flag remains true.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read.
Reason for missing information: The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read.
Required materials and conditions: Original plans for three measures, time points, models, tests and multiplicity handling
Materials to obtain first: The parent's split-results wording is not turned into a new claim that all three measures were the parent's clinical coprimary endpoints. Multiplicity-adjustment details have not been read.
Further research: Obtain the DNA analysis's original outcome list, time points, tests, adjustments and selective-reporting plan.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original plans for three measures, time points, models, tests and multiplicity handling
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N16 · Is the absence of a clinical minimum-effect threshold and prespecified success boundary preserved?

Current findings: The original account records no clinical minimum-effect threshold or prespecified success boundary and describes the effects as small.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects.
Reason for missing information: Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects.
Required materials and conditions: Clinical validation, minimum-effect thresholds and plans for each measure
Materials to obtain first: Statistical positivity is not converted into certification of general clinical importance, calorie targets or health effects.
Further research: Connect clinical validation, prespecified thresholds and plans for each measure if provided.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Clinical validation, minimum-effect thresholds and plans for each measure
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

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N17 · What is the original scope of allocation and analyst blinding?

Current findings: The Korean account says that analysts did not know allocation; the English account specifies 'laboratory analysts blinded'. The parent's 2:1 randomized design is also preserved.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read.
Reason for missing information: Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read.
Required materials and conditions: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures
Materials to obtain first: Blinding of all analysts, participants or intervention providers is not newly certified. Allocation concealment and measure-specific model procedures have not been read.
Further research: Obtain original allocation, laboratory and measure-analysis methods and blinding roles.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Parent allocation, blinding of DNA laboratory staff or analysts, and analysis procedures
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

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N18 · Is the relationship between achieved restriction, adherence, weight changes and measure effects directly verified?

Current findings: The 25% target and average achieved restriction of about 12% are preserved as historical study conditions.
Verification status: Unverified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms.
Reason for missing information: Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms.
Required materials and conditions: Original achieved exposure, adherence, concurrent changes and effects of interest
Materials to obtain first: Effects of individual achieved restriction, time-specific adherence and weight or nutrient mediation are not newly calculated or confirmed as causal mechanisms.
Further research: Obtain achieved exposure, adherence, concurrent changes and prespecified mediation or effect-of-interest material.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Original achieved exposure, adherence, concurrent changes and effects of interest
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N19 · Do gaps remain concerning persistence after 12 or 24 months, mechanisms and other aging measures?

Current findings: The original DNA effects are presented at 12 and 24 months, and the intervention lasted two years.
Verification status: Unverified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in.
Reason for missing information: Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in.
Required materials and conditions: Follow-up measures, duration, denominators, original effects and direct mechanism evidence
Materials to obtain first: Persistence after the intervention or effects on all aging mechanisms and later measures are not newly filled in.
Further research: Obtain direct post-intervention follow-up and original measurements, denominators and effects separately by measure.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Follow-up measures, duration, denominators, original effects and direct mechanism evidence
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

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N20 · Has the result been kept separate from disease, disability, death, lifespan and independent-living outcomes?

Current findings: The original account explicitly states that reduced disease, disability or death was not measured and longer healthy life was not answered.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living.
Reason for missing information: The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living.
Required materials and conditions: Direct clinical endpoints, adequate follow-up, events, denominators and effects
Materials to obtain first: The slowing signal is not turned into proof of clinical rejuvenation, added years of life or maintained independent living.
Further research: Direct definitions, long-term follow-up, denominators and effect data are needed for each clinical outcome.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Direct clinical endpoints, adequate follow-up, events, denominators and effects
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N21 · Are the two sibling sheets, two time points and one post hoc report kept from being independently summed?

Current findings: Both sheets share the same CALERIE post hoc report and the 220-person and 197-person context.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded.
Reason for missing information: Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded.
Required materials and conditions: Relationships among the parent trial, post hoc report, same participants, measures and time points
Materials to obtain first: Reports, measures and time points are not summed as new independent trials or participant totals. Unique trial and participant totals and the final independent count remain unrecorded.
Further research: Link additional reports through original trial identifiers while retaining relationships to the same population.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Relationships among the parent trial, post hoc report, same participants, measures and time points
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N22 · Are funding and DunedinPACE invention and commercial-licensing interests distinguished?

Current findings: Support from NIA, American Brain Foundation, CIHR and others, authorship by inventors D.L. Corcoran and D.W. Belsky, and commercial licensing are preserved.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read.
Reason for missing information: Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read.
Required materials and conditions: Funding, authors, invention, licensing, provision and analysis roles
Materials to obtain first: Inventors are not newly classified as company employees or financial beneficiaries. Details of cash funding, provision, affiliations and outside analysis have not been read.
Further research: Obtain original funding, licensing, affiliations, product or service provision, analysis and manuscript roles separately.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Funding, authors, invention, licensing, provision and analysis roles
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

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N23 · Does absent safety reporting establish that the parent trial had no harms?

Current findings: This post hoc analysis did not report safety as an endpoint, and the parent's safety assessment is Unknown.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE.
Reason for missing information: Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE.
Required materials and conditions: Harm plans, events by group and exposure denominators for this analysis and the parent trial
Materials to obtain first: Absent reporting in the post hoc report is not extended to zero adverse events or established safety across CALERIE.
Further research: Obtain the parent trial's original harm plans, events by group, exposure, discontinuation and denominators separately.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Harm plans, events by group and exposure denominators for this analysis and the parent trial
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N24 · Do gaps remain concerning long-term or rare harms under two-year achieved exposure?

Current findings: The original safety account states that this analysis cannot determine harms of long-term caloric restriction.
Verification status: Unverified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented.
Reason for missing information: Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented.
Required materials and conditions: Direct harm data by achieved exposure, discontinuation, severity and duration
Materials to obtain first: Duration alone does not establish safety, and new harm counts, rates, CIs or nutritional problems are not invented.
Further research: Obtain group-specific harms, discontinuation, rare events and long-term data from the parent trial and follow-up reports.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Direct harm data by achieved exposure, discontinuation, severity and duration
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N25 · Are harm replication, applicability to other populations or exposures, and dietary instructions distinguished?

Current findings: The current population is healthy non-obese adults, and the historical exposure is a two-year study with differing target and achieved average restriction.
Verification status: Unverified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created.
Reason for missing information: Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created.
Required materials and conditions: Direct effects, harms, exposures and same-population relationships by population
Materials to obtain first: Effects or harms in other populations or dietary-restriction methods are not newly confirmed, and personal calorie, diet or weight-loss instructions are not created.
Further research: Connect direct comparisons and harm evidence for new populations or exposures separately.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Direct effects, harms, exposures and same-population relationships by population
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N26 · Are the stored summary, PubMed link and registration identifier distinguished from materials actually read?

Current findings: The whole parent summary was read for production, and the original PubMed link and NCT00427193 identifier were connected.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested.
Reason for missing information: A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested.
Required materials and conditions: Separate access records for the summary, abstract, full text, registration, protocol and SAP
Materials to obtain first: A new registration URL is not constructed from the identifier; all external materials remain unread. Links and original full text were not compared or tested.
Further research: Connect additional provided material with its individual access status.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Separate access records for the summary, abstract, full text, registration, protocol and SAP
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

Related sources R01

N27 · Are original dates, Korean and English text, empty values, subclaim and parent values, and review status preserved?

Current findings: The 2026-08-26 reference date, empty correction and deliberation values, Korean and English text, C54, original axes and subclaim C are preserved. Original pending and production-eligible markers are historical; content review at that time remained incomplete.
Verification status: Partly verified
Materials actually read: Summary read; external materials not read
Why unverified: Only the relevant information from the stored summary is recorded. Detailed original materials have not been read, and the original content review remains incomplete. The missing subclaim score and unrecorded precision are not filled in. Original model, content and scope review activation and completion remain false; added assessment units are 0 and the final independent count is unrecorded.
Reason for missing information: The missing subclaim score and unrecorded precision are not filled in. Original model, content and scope review activation and completion remain false; added assessment units are 0 and the final independent count is unrecorded.
Required materials and conditions: Distinction among the complete original, selected assessment record, history and current production status
Materials to obtain first: The missing subclaim score and unrecorded precision are not filled in. Original model, content and scope review activation and completion remain false; added assessment units are 0 and the final independent count is unrecorded.
Further research: Proposal: Reflect additional materials and decisions through preservation of original wording and separate events.
Remaining uncertainty: Unread/unverified does not mean zero effect, zero events, safety or new clinical certification.
Conditions for verification: Distinction among the complete original, selected assessment record, history and current production status
Why this condition is needed: An individual condition for recording the selected measure, time, original values and applicability limits
Application exceptions: Unread external materials, other measures or out-of-scope outcomes do not establish that a condition is met, an effect is zero or safety is established.
Referenced methods: Slower DunedinPACE

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