| 1 |
Met |
Full text not readStored summary read |
N01 · Independent claimWhich actual B12 regimens are being compared for day-90 Hb?Required (selected day-90 Hb comparison) |
The question is whether the actual oral regimen of swallowing Dodex cyanocobalamin ampule+fruit juice raises day-90 Hb more than same-schedule IM in adults with B12-deficiency megaloblastic anemia. The subclaims list is actually empty. Efficacy versus no treatment, equivalence and noninferiority were not made the question. |
Verification that the boundary is preserved; not establishment of superiority or certification of efficacy for all B12 products. |
The original question of day-90 Hb in adults with laboratory-confirmed B12-deficiency megaloblastic anemia: oral ampule+fruit juice versus the same compound IM |
Identify direct comparisons within this boundary, and treat other forms, populations and endpoints as separate questions. |
| 2 |
Partly verified |
Full text not readStored summary read |
N02 · Chemical form and productIs the cyanocobalamin product distinguished from unverified manufacturing details?Required (selected day-90 Hb comparison) |
Retained S01 specifies Dodex(Deva, Turkey) cyanocobalamin 1000mcg ampules. Manufacturing origin, batch, purity, additional salt and release specifications are not reported. Other B12 chemical forms and oral tablets were not substituted. |
The product/ingredient is reported, but manufacturing, batch, additional chemical-form/release details and a current comparison with the original PDF remain unverified. |
Documentation of the original Dodex/Deva product's active ingredient, manufacturing origin, batch, purity, additional salt and release specifications |
Compare the original trial product documentation and batch/ingredient records with actual administration records. |
| 3 |
Met |
Full text not readStored summary read |
N03 · Actual route and physical formulationIs oral ampule+fruit juice being read as a tablet comparison or an isolated-route comparison?Required (selected day-90 Hb comparison) |
The retained original regimen compares oral administration of the same cyanocobalamin ampule contents mixed into 20mL fruit juice and swallowed with IM administration. It is not a tablet, sublingual, intranasal or intravenous regimen. Fruit juice is specified only for the oral arm, so this does not establish pharmacokinetic equivalence of the routes in isolation. |
Verification of the criterion distinguishing the currently retained regimens. This is not new verification of the original administration documents or pharmacokinetics. |
The original S01 section on oral ampule contents/20mL fruit juice, the same IM product and actual administration methods |
Check the original administration section and product records, and design an isolated-route/formulation comparison separately. |
| 4 |
Partly verified |
Full text not readStored summary read |
N04 · Nominal dose and cumulative doseIs the 1000mcg schedule distinguished from the exact 90-day total?Required (selected day-90 Hb comparison) |
The nominal schedule for both arms is 1 time at 1000mcg, daily for 10 days→1 time per week for 4 weeks→1 time per month. The 14000mcg for the first 14 administrations is the historical subtotal; the exact 90-day cumulative dose remains unverified. No cumulative-dose calculation or recommended dose was created in this review. |
The nominal dose/schedule is retained, but exact administration dates and total dose over 90 days, and actual exposure, have not been verified. |
Nominal dose for 1 time in each arm, daily/weekly/monthly schedules, administration dates throughout 90 days and actual total dose |
Link original prescription/administration dates and actual doses taken in each arm to the time points and denominators. |
| 5 |
Unverified |
Full text not readStored summary read |
N05 · Actual adherence and concurrent exposureHave actual doses taken and dietary/concurrent B12 been verified?Required (selected day-90 Hb comparison) |
Quantitative adherence and total dietary, fortified-food and concurrent B12 exposure could not be verified in the retained source. The planned schedule alone was not described as verifying balance in actual exposure or the effect of adherence. |
The link between actual exposure/adherence and the analysis remains unverified. |
Arm-specific adherence/missed administrations, diet, fortified foods, concurrent B12 and exposure records and analyses |
Compare arm-specific dosing/missed administrations and dietary/concurrent exposure with the effects of assignment/adherence. |
| 6 |
Met |
Full text not readStored summary read |
N06 · Observation periodIs 90-day observation separated from the lifelong monthly plan?Required (selected day-90 Hb comparison) |
Observation lasted 90 days. A lifelong administration plan of 1 time per month is not a record of lifelong observation. This question and the original values were restricted to 90 days. |
Verification of the boundary between the retained plan and observation; not verification of long-term efficacy or safety. |
Distinguishing S01 administration, visits/end of observation and monthly maintenance plans from actual follow-up |
When asking about maintenance or effects after discontinuation, obtain actual long-term follow-up and its denominators separately. |
| 7 |
Met |
Full text not readStored summary read |
N07 · Actual population and cutoffsWhich adults with B12-deficiency anemia were compared?Required (selected day-90 Hb comparison) |
The actual S01 participants were nonpregnant, nonlactating adults aged 32–87, reported to have B12<160pg/mL, MCV>94fL and megaloblastic anemia; baseline Hb in the analyzed groups was <12g/dL. This was not extended to the general population with normal B12, children or pregnancy/lactation. |
Verification of the retained population definition; this does not imply the same effect in all adults or special populations. |
Inclusion/exclusion for ages 32–87, nonpregnant/nonlactating status, B12<160pg/mL, MCV>94fL, megaloblastic anemia and Hb<12 in the analyzed groups |
Link original eligibility, baseline distributions and exclusions to the actual denominators of the direct comparison. |
| 8 |
Partly verified |
Full text not readStored summary read |
N08 · Causes and iron/folate statusIs the entire cohort being called confirmed pernicious anemia, or are cause-specific Hb results being invented?Required (selected day-90 Hb comparison) |
Dietary and gastric causes, suspected malabsorption and unverified causes are mixed. Intrinsic-factor testing was not performed, and the entire cohort was not described as confirmed pernicious anemia. Folate was reported as normal, but iron status and cause-specific Hb were not reported. |
Mixed causes and folate information are retained, but confirmation by cause, iron status and Hb comparisons remain unverified. |
Dietary/gastric, malabsorption and unverified causes; intrinsic-factor testing, iron/folate status and cause-specific Hb |
Review causes/baseline tests and prespecified stratified Hb comparisons with the actual denominators. |
| 9 |
Partly verified |
Full text not readStored summary read |
N09 · Comparator, concomitant treatment and rescue treatmentCan the same IM schedule be distinguished from common anemia treatment?Required (selected day-90 Hb comparison) |
The active comparator is the same Dodex1000mcg IM with the same loading/weekly/monthly schedule. Iron, folate, transfusion, erythropoietin and rescue treatment remain unverified; fruit juice is specified only for oral administration. This was not converted into an untreated comparator. |
The actual active comparator is retained, but balance in background/rescue treatment between arms and the oral regimen's contribution remain unverified. |
Actual records of the same Dodex IM, arm-specific iron/folate/transfusion/EPO, rescue treatment/changes, adherence and fruit juice |
Compare arm-specific background treatment, changes/rescue records and the analysis of the Hb effect of interest. |
| 10 |
Partly verified |
Full text not readStored summary read |
N10 · Hb measurementIs the objectivity of Hb the same as verification of actual testing and assessor blinding?Required (selected day-90 Hb comparison) |
Hb is an objective laboratory measure in g/dL, but Hb analyst blinding remains unverified. Endoscopy blinding was not transferred to Hb assessment. Hb is distinct from fatigue, transfusion, death and daily functioning. |
The endpoint/unit is available, but comparison against the original source for Hb testing implementation, assessors and arm-specific measurement limitations is incomplete. |
Hb(g/dL) assay method/time points, measurements by arm, analyst blinding and missing measurements/errors |
Compare the original assay section with Hb assessment/time points and denominators by arm. |
| 11 |
Partly verified |
Full text not readStored summary read |
N11 · Endpoint and day-90 hierarchyIs an article-stated primary Hb endpoint the same as a registry-verified unique primary visit?Required (selected day-90 Hb comparison) |
Hb is one of the article-stated primary endpoints, and day 90 is the last planned and reported response assessment. It is not a registry-verified unique prespecified primary time point. The difference whereby day 90 is absent from the abbreviated Methods CBC visit list but present in the response criteria/table at day 90 is preserved. |
Timing information is available in the article/table, but verification against the plan of the prespecified hierarchy, multiplicity and differences in the lists remains incomplete. |
Original Response Criteria/table, CBC visit list and endpoint/time-point hierarchy in the registry/protocol/SAP |
Compare the original plan/visit schedule and registry amendment history with the actually reported day-90 assessment. |
| 12 |
Met |
Full text not readStored summary read |
N12 · Arm-specific Hb and SDAre arm-specific Hb means/SDs at baseline and day 90 linked without changing their values?Required (selected day-90 Hb comparison) |
Retained Hb mean(SD) values are oral baseline 8.4(2.1)→day 90 13.8(0.7), and IM 8.3(2.3)→13.7(0.9) g/dL. The analyzed denominators are oral 26/IM 34; SD was not changed to SE, and no new calculations were performed. |
Verification of exact preservation and attribution of the numbers; not a visual verification of the publisher PDF in this review. |
Oral/IM baseline and day-90 means(SD), g/dL and analyzed denominators 26/34 in the original S01 table |
When checking the original table/transcription's numbers, definitions of dispersion and denominators at each time point, preserve and compare all before/after values. |
| 13 |
Met |
Full text not readStored summary read |
N13 · Unadjusted endpoint differenceFor which between-group effect is +0.10g/dL the retained calculation?Required (selected day-90 Hb comparison) |
Oral−IM +0.10g/dL is the historically reconstructed unadjusted day-90 endpoint mean difference. It was explicitly substituted because the prioritized adjusted/change estimate was unavailable; it was not labeled a prespecified NI analysis or the original Mann–Whitney test. |
Verification that the existing calculation's definition and provenance are preserved; not a new efficacy calculation or certification of a prespecified analysis. |
Direction and calculation provenance of the unadjusted day-90 endpoint mean difference, and absence of the prioritized adjusted/change effect |
If the original adjusted/change estimand becomes available, compare its definition and values in a separate version. |
| 14 |
Met |
Full text not readStored summary read |
N14 · Within-group change and causalityAre +5.4 in both arms and a rounded change difference of 0 being read as no effect/equivalence?Required (selected day-90 Hb comparison) |
Rounded within-group mean increases are approximately +5.4g/dL in both arms; the rounded change difference of 0 is descriptive. Within-group improvement is not an effect versus no treatment, and a change difference of 0 does not verify equivalence or no effect. The corresponding establishment flags in the original interpretation are false. |
Verification of the criteria for preserving interpretive boundaries and historical values; not a reassessment of the clinical conclusion. |
Rounded within-group changes, between-group effects, change variance/CI and definition of the comparison |
Check the original change-score variance/between-group CI and analysis, and review them separately from endpoint-value results. |
| 15 |
Unverified |
Full text not readStored summary read |
N15 · Adjusted and change estimatesWere the adjusted endpoint difference and change-score uncertainty reported?Required (selected day-90 Hb comparison) |
adjusted_effect, change_score_CI and reported_exact_between_group_P are empty. Baseline adjustment, change variance and P values were not calculated in this review. The unadjusted endpoint reconstruction does not resolve these gaps. |
The original values/definitions of the prioritized adjusted/change analysis and exact between-group test remain unverified. |
Baseline-adjusted endpoint effect/model, change SD/CI, analysis population and handling of missing data |
Obtain the original analysis/supplement, arm-specific paired-change variance/covariance and handling of missing data. |
| 16 |
Partly verified |
Full text not readStored summary read |
N16 · Reconstructed CIAre the exact values, provenance and interpretive limitations of the 95% CI preserved?Required (selected day-90 Hb comparison) |
The historical exact values of editor_reconstructed_CI95 are [-0.313492,0.513492]g/dL, displayed as −0.31~+0.51. This is not the original Mann–Whitney/NI analysis; it includes 0 and differences in both directions. Without a clinical margin, it does not exclude meaningful benefit. |
The reconstructed interval is retained, but the originally reported/adjusted and change intervals and a justified clinically important difference remain unverified. |
C02 editor-reconstructed endpoint-difference CI, original arm-specific SDs/denominators, calculation conditions and clinically important difference |
If the original estimate/interval and calculation definition become available, separately compare arm-specific denominators/dispersion and clinical criteria. |
| 17 |
Unverified |
Full text not readStored summary read |
N17 · Clinical importanceIs there a verified Hb MCID/important difference?Required (selected day-90 Hb comparison) |
verified_between_group_MCID is empty. Historical Hedges g0.12039708 or E~ represents magnitude under statistical conventions only; it does not verify failure to meet an MCID, a clinically positive result or exclusion of important benefit. |
A justified clinical-importance criterion for the selected between-group Hb difference remains unverified. |
A justified important between-group difference for the selected B12-deficiency anemia, day-90 Hb and active comparator |
Obtain evidence of importance for this population/scale/time point and compare it separately with the relevant effect/CI. |
| 18 |
Partly verified |
Full text not readStored summary read |
N18 · Superiority, equivalence and NIWas the authors' interpretation of similarity converted into verified equivalence?Required (selected day-90 Hb comparison) |
The authors interpreted the routes as similarly effective, but prespecified equivalence/NI margins and requirements remain unverified. formal_Hb_NI_margin is empty, and establishment of superiority, equivalence, NI and no effect was retained as false. |
The original interpretation exists, but the formal evidence for equivalence/NI and requirements for establishing superiority have not been verified. |
Original authors' interpretation, superiority/equivalence/NI design and prespecified margins/analysis requirements |
If an NI/equivalence question is separately assigned, review its prespecified margin, analysis and precision against the relevant requirements. |
| 19 |
Partly verified |
Full text not readStored summary read |
N19 · Allocation and completer denominatorsWhich denominators do 70/10/26/34 each represent?Required (selected day-90 Hb comparison) |
After 70 participants were enrolled, 10 lost to follow-up after day10 were excluded, and oral 26/IM 34 were analyzed. Original allocation denominators by arm remain unverified. Completer counts were not used as initial allocation counts, and the 10/70 dropout rate was not newly calculated. |
Total enrollment/losses and completer counts are available, but original allocation by arm and measurements/analyses at each time point remain unverified. |
70 enrolled, 10 lost to follow-up after day10, oral 26/IM34 analyzed, original allocation by arm and numbers measured at each time point |
Link the original flow diagram, arm-specific visit/analysis denominators and handling of missing data to the outcome of interest. |
| 20 |
Unverified |
Full text not readStored summary read |
N20 · Missing data and analysis populationCan the effect of assignment/ITT be verified from completer results?Required (selected day-90 Hb comparison) |
The current result is a 90-day completer analysis. Arm-specific reasons/distribution for the exclusion of 10 participants and ITT, imputation and sensitivity analyses have not been verified. Completer analysis was not automatically designated an effect of assignment or PP. |
Detailed evidence on the relevance of missing data, the effect of assignment and the analysis population/handling remains unverified. |
Reasons for losses/distribution by arm, relationship to outcomes, ITT/imputation, sensitivity/PP definitions and estimand |
Obtain arm-specific losses/original outcomes, the planned analysis and sensitivity analyses for missing data. |
| 21 |
Partly verified |
Full text not readStored summary read |
N21 · Design and allocationHave both block randomization and implementation of concealment been verified?Required (selected day-90 Hb comparison) |
S01 is a single-center prospective randomized open-label active-control trial and reports block randomization. Implementation of allocation concealment is not reported. No official RoB/GRADE assessment was performed in this review, and concealment failure was not established. |
Design/allocation is reported, but verification of actual concealment, implementation and baseline comparisons remains incomplete. |
Single-center parallel active-control design, block allocation/concealment implementation, baseline balance and original Methods |
Compare original allocation implementation and baseline balance with the Hb outcome of interest. |
| 22 |
Partly verified |
Full text not readStored summary read |
N22 · Open-label regimens and measurementWere the limitations of open-label routes and the objectivity of Hb reviewed separately?Required (selected day-90 Hb comparison) |
In the open-label route comparison, oral administration involved fruit juice and IM was nurse-administered. Hb is an objective test, but analyst blinding/concomitant treatment remain unverified. Endoscopy blinding was not borrowed, and the trial was not automatically classified as failed or unbiased. |
The actual open-label/assessment context is retained, but implementation details concerning changes and measurement remain unverified. |
Patient/clinician/assessor blinding, administration differences, Hb measurement and changes in concomitant treatment |
Compare route-specific care, changes in concomitant treatment and implementation of Hb assessment against the original records. |
| 23 |
Unverified |
Full text not readStored summary read |
N23 · Registration, protocol and SAPWere S01's prespecified plan and actual results compared?Required (selected day-90 Hb comparison) |
S01 preregistration, protocol/SAP and the unique primary-visit hierarchy remain unverified. The S23–S26 shells or the OB12 protocol were not used as the S01 plan. Failure to obtain material does not establish nonregistration or selective reporting. |
Material for comparing prespecified plans, multiplicity and selection/changes for the Hb outcome of interest remains unverified. |
S01 registration, protocol, SAP, primary time point/analysis, multiplicity and amendment history |
After verifying identity, compare S01's actual registration/plan/history with its Hb reporting. |
| 24 |
Met |
Full text not readStored summary read |
N24 · Reports and trial familiesAre 28 original articles, index records and reviews being counted as 28 replications?Required (selected day-90 Hb comparison) |
S01/S02 belong to TF-BOL2003 with the same DOI10.1016/S0149-2918(03)90096-8 and PMID14749150. S04/S05 are the OB12 original article/protocol; S27 is a supplementary lead. The 28 bibliographic records include reviews, safety/labels and registry attempts, so they were not counted as 28 trials. |
Verification that report overlap/roles are distinguished; unique independent trial and participant counts across all 28 reports were not newly established. |
The same DOI/PMID for S01/S02, OB12 original article/protocol/supplementary leads, report types and family links |
Verify each report's family identity by comparing original registration, institutions/recruitment periods and participant overlap. |
| 25 |
Unverified |
Full text not readStored summary read |
N25 · Replication of the same questionAre other B12 studies being called replications of the same day-90 Hb result?Required (selected day-90 Hb comparison) |
The retained decisive direct family is TF-BOL2003 alone; R1 is the internal code for that narrow boundary. Replication of the exact same claim could not be verified. Differences in other populations/forms/endpoints were not converted into R0, and no new replication count was calculated. |
Independent replication of this actual regimen/population/endpoint at 90 days remains unverified within the current retained scope. |
Unique direct comparisons matching the population, product, route, active comparator and day-90 Hb/denominators |
If a new directly eligible comparison is authorized/obtained, compare family-specific criteria and opposing results together. |
| 26 |
Met |
Full text not readStored summary read |
N26 · Favorable opposing evidenceAre Gupta2025's favorable Hb results and the reason for exclusion both present?Required (selected day-90 Hb comparison) |
Gupta2025's favorable Hb results are preserved, but were not combined with this claim because there was no confirmed B12-deficiency anemia stratum. Retain the historical selected S06 PDF pages and locations: p721 eligibility/common IFA, p724 Hb and p726 safety/funding/registration. |
Verification of preservation of positive evidence and reasons for exclusion; not new verification of S06 numerical results or full text in this review. |
S06 Hb results in anemic women, confirmed B12-deficiency anemia stratum/background IFA, product/denominators/duration |
Compare original S06 eligibility, strata/product/background treatment and exact Hb results as a separate eligibility question. |
| 27 |
Met |
Full text not readStored summary read |
N27 · Unfavorable opposing evidenceAre Tandon2022's results unfavorable to oral treatment and the reason for pediatric exclusion present?Required (selected day-90 Hb comparison) |
Tandon2022's Hb results unfavorable to oral treatment are preserved, but were not combined with this adult claim because it was a pediatric trial. Historical access to only lines40–44 of the original S13 abstract was not converted into current full-text verification. |
Verification of preservation of unfavorable evidence and the population-based reason for exclusion. Do not combine it as direct contradiction or replication in adults. |
S13 pediatric nutritional megaloblastic anemia, direction of Hb findings in the original abstract and difference from the adult boundary |
Obtain the population/regimen/time points, denominators and results within their original scope, and link them to a separate pediatric question. |
| 28 |
Met |
Full text not readStored summary read |
N28 · Adjacent endpoints and routesAre serum B12, Hct and other routes substituting for the selected Hb outcome?Required (selected day-90 Hb comparison) |
Hct in S03, serum B12 normalization NI in OB12 S04/S05, biomarkers/preferences in S07, RYGB in S08, metformin/Sucrosomial serum B12 in S12 and 3 non-oral routes in S14 differ from the selected day-90 Hb outcome. The relevant bibliography/access levels were preserved, and no new Hb results were created. |
Verification explaining the applicability boundaries of the question/materials; not an efficacy reassessment of adjacent studies. |
Roles of reports on Kuzminski Hct, OB12 serum normalization, metabolism/preferences/RYGB and other forms/intranasal/IV administration |
After actually obtaining each original Methods/table and population-specific Hb results, separately review whether it addresses the same question. |
| 29 |
Partly verified |
Full text not readStored summary read |
N29 · Reviews and unaccessed leadsWere review summaries/registry shells used as original trial results?Required (selected day-90 Hb comparison) |
Preserve the historical scope: S09 abstract/full text inaccessible, S10 conference bibliography/results inaccessible, S11 indexed excerpt, S15 official summary/full review inaccessible, S17 first PDF page, and S19 excerpt favoring injections for Hb/underlying trial unverified. S23–S26 are JS shells, S27 an unopened supplementary lead, and S28 an article's CTRI mention without an obtained official record. |
Leads/review roles exist, but comparison of unaccessed original results, registry plans/history and underlying families remains unverified. |
Material types and reading scope for unaccessed S09–S11, reviews/evidence tables S15–S19 and registry/supplementary leads S23–S28 |
In an authorized update, compare identities, content and families of original reports, official registry records and supplements. |
| 30 |
Unverified |
Full text not readStored summary read |
N30 · Funding and product supplyDoes I1 verify actual mixed funding or independence?Required (selected day-90 Hb comparison) |
S01 funding sources and product supply remain unverified. I1 is an internal rule-based value for unverified funding, not proof of mixed funding. Author employment/patents, absence of disclosed COI and independent funding were not inferred. |
Original disclosures of independence/conflicts of interest and product-supply materials remain unverified. |
S01 research funding, product supply, author disclosures/institutions and original Funding/COI |
Check original S01 funding/supply, author disclosures, relevant institutions and family information. |
| 31 |
Met |
Full text not readStored summary read |
N31 · Historical assessment and methodsAre C, 46, E~ and the empty precision value being read as a new assessment or an MCID?Required (selected day-90 Hb comparison) |
Leave historical efficacy C, 46, Caution and B/S/R1/I1/E~/B2/empty precision unchanged. E~ is not proof of failure to meet an MCID or statistical positivity; empty precision does not mean no CI. Document quality A and single-assistant self-review are not independent clinical/GRADE certification. |
Verification of preservation of historical values and methodological interpretation boundaries; not a new efficacy, safety or grade assessment. |
Boundaries of the original grade/score/Caution, axes, document quality A, self-review and method implementation |
If an individual correction is authorized, review it as a separate event preserving the complete original assessment, before/after values and reasons. |
| 32 |
Met |
Full text not readStored summary read |
N32 · Current and historical readingIs this review's summary reading distinguished from historical full-text transcription access?Required (selected day-90 Hb comparison) |
Reading in this review covers the current 3113 stored summary's 17 KO fields, structure/1 evidence entry and 28 bibliographic/historical access records. The historical 2026-09-16 scope, including the S01 repository full-text transcription, selected S06 PDF pages, the first S17 PDF page and official safety documents, was not converted into current external reading. Summary links connect to actual values/pointers/stored-summary SHA. |
Verification distinguishing current from historical reading and summaries from original full texts. Not verification of current external original bytes/full texts. |
Exact pointers in the currently stored manuscript, 28 bibliographic records/locations and historical material types/access levels/dates |
If original-material acquisition/actual reading is authorized, separately record the edition, sections read and file SHA for each material type. |
| 33 |
Unverified |
Full text not readStored summary read |
N33 · Original PDF/transcription comparisonHas a current visual comparison with the publisher PDF been performed?Required (selected day-90 Hb comparison) |
Historical S01 access was to a repository full-text transcription. Visual comparison with the publisher PDF remains unresolved; the original PDF, old ZIP, calculation log and transcription were not newly opened in this review. The stored manuscript SHA was not described as the original article PDF SHA. |
A current visual comparison of the original publisher PDF with the transcription, numerical values and hierarchy remains unverified. |
Original publisher PDF, repository transcription, tables/units/footnotes and a visual-comparison event |
After authorized/lawful acquisition of the original PDF, compare actual tables, footnotes and text against the transcription and record the edition/hash. |
| 34 |
Met |
Full text not readStored summary read |
N34 · Search, registration and publication statusAre gaps in the current retained scope being described as absence of current studies?Required (selected day-90 Hb comparison) |
The evidence cutoff is 2026-09-16, and the actual review date recorded here is 2026-10-05. Original audit/search_log and access_log paths/summaries and the absence of subscription Embase/Scopus searches or complete exports are historical. New clinical searches/registry/correction queries for 3113 in this review total 0; gaps were not converted into absence of studies. |
Verification of the criterion distinguishing the cutoff date and review scope; not a current exhaustive check of existence, corrections or retractions. |
Evidence cutoff 2026-09-16, original search/access summaries, actual reading in this review and scope regarding unpublished material/corrections/retractions |
In a separately authorized update, record actual search expressions, scope, failures and original responses for searches/registration/corrections as a new event. |
| 35 |
Partly verified |
Full text not readStored summary read |
N35 · Harm definitions and collectionDoes no reported treatment-related adverse reaction mean total AE0?Required (selected day-90 Hb comparison) |
The original statement is a 90-day record for oral 26/IM34 that no treatment-related adverse reactions were reported. Separate accounting and collection methods for all AEs, SAEs and AE-related discontinuations remain unverified; this was not converted into all AE0. |
A treatment-related narrative is available, but total-event definitions, systematic collection, severity and discontinuation accounting remain unverified. |
S01 treatment-related AE definition, collection method, all AEs/SAEs, discontinuations, severity and original denominators |
Check the original Tolerability section, collection/adverse-event tables and discontinuation/loss records. |
| 36 |
Partly verified |
Full text not readStored summary read |
N36 · Safety denominators and lossesDoes safety coverage include the 10 participants outside the 26/34 completers?Required (selected day-90 Hb comparison) |
Link the treatment-related AE narrative to the oral 26/IM 34 analyzed at 90 days. Safety of the 10 participants lost after day10 remains unverified. It was not stated that all events were collected for all 70 enrolled participants or that event incidence was 0. |
Analysis duration and completer counts are available, but the total safety denominator, events among lost participants, exposure time and incidence remain unverified. |
Total exposure/safety denominators, numbers of affected people/events, 90-day/early follow-up and safety of the 10 lost participants |
Link arm-specific exposure/safety analysis counts, reasons for losses/events and follow-up duration to the original records. |
| 37 |
Unverified |
Full text not readStored summary read |
N37 · Harms: timing, comparison and alternativesDoes a no-event narrative verify comparative safety or causal safety of oral treatment?Required (selected day-90 Hb comparison) |
There is a narrative that no related AEs were reported in both arms, but detailed information on event onset/recovery, re-exposure, overall comparative risk, concomitant treatment and safety among lost participants remains unverified. Untreated background incidence and causal safety of oral treatment were not inferred. |
Events/timing, alternative explanations and denominators for actual comparative harms remain unverified. |
Arm-specific events; timing of exposure, onset, discontinuation and recovery; IM comparator; concomitant treatment; baseline/loss-related alternative explanations |
Check material that permits comparison of original arm-specific events/timing with concomitant treatment, baseline risks and missing data. |
| 38 |
Partly verified |
Full text not readStored summary read |
N38 · Official safety materials and independent eventsAre official notices/labels being counted as independent clinical replications of harms?Required (selected day-90 Hb comparison) |
S20 official explanatory material, S21 cyanocobalamin/hydroxocobalamin cobalt notice and S22 cyanocobalamin injection label are historical materials. These 3 documents were not counted as 3 independent harm trials/events, and current underlying material was not newly verified in this review. |
The types/boundaries of official materials are retained, but independent events, denominators/causes and comparison with current editions remain unverified. |
Material types/molecules, underlying events, denominators and families for S20 ODS, S21 cobalt notice and S22 injection label |
In an authorized update, compare notice versions, original events/denominators and relationships among repeated citations. |
| 39 |
Met |
Full text not readStored summary read |
N39 · UL and safety interpretationDoes an unset UL guarantee unlimited safety?Required (selected day-90 Hb comparison) |
In retained S20, no established B12 UL does not guarantee unlimited safety. The original Caution safety label was retained; the study dose/schedule was not made into instructions for personal dosing, injection choice, transfusion or medication changes. |
Verification of preservation of the scope of safety interpretation; not absence of harm or certification of personal safety. |
S20 B12 UL explanation and reasons for no established UL; boundaries of the selected regimen's duration/population and actual events |
If asking about safety by dose, duration or vulnerable population, review the relevant direct evidence under separate criteria. |
| 40 |
Partly verified |
Full text not readStored summary read |
N40 · Cobalt and injection warningsWere the label's chemical form/route transferred into oral-treatment incidence?Required (selected day-90 Hb comparison) |
Link cobalt sensitivity to the verified cyano/hydroxo notice. Leber and early hypokalemia during intensive treatment of severe megaloblastic anemia fall within the cyanocobalamin injection-label scope. These were not converted into incidence for oral treatment/other chemical forms or observed S01 events. |
Original warnings/scope are retained, but direct incidence for the selected oral regimen and harms in special populations remain unverified. |
S21 scope of cobalt sensitivity for cyano/hydroxo; S22 injection context for Leber/early hypokalemia |
Check original label/notice editions and underlying events separately from direct oral-treatment/special-population evidence. |
| 41 |
Unverified |
Full text not readStored summary read |
N41 · Long-term harms and vulnerable populationsDo short-term adult data answer questions about rare harms or long-term/special-population safety?Required (selected day-90 Hb comparison) |
Do not establish long-term safety or safety in hepatic or renal disease, pregnancy/lactation or children from this trial. The 90-day adult completer data do not prove safety regarding rare events or beyond follow-up; the original Caution was retained. |
Direct evidence on harms/vulnerable populations outside the selected 90-day scope remains unverified within the current retained materials. |
Long-term/rare events, exposure/baseline risk in hepatic or renal disease, pregnancy/lactation and children, denominators and suitable designs |
If a safety extension is requested, separately review observational/comparative data appropriate to the population, duration and events. |
| 42 |
Not applicable |
Full text not readStored summary read |
N42 · Direct dose optimizationMust a same-schedule comparison also answer the optimal-dose question?Extension boundary; required for an optimal-dose claim |
This is a 90-day Hb comparison with the same nominal 1000mcg schedule in both arms, not a dose-selection/response question. Optimal-dose evidence was not required to complete this question, and no effective recommended dose was newly created. |
Extension to optimal dosing does not apply to the currently fixed question; this is not replacement of gaps in actual exposure, adherence or total dose with NA. |
If an optimal-dose question is added: direct dose/active-amount comparisons, actual exposure and Hb/harm estimates |
If optimization is separately requested, design direct dose contrasts and harm assessment in the same population/product. |
| 43 |
Not applicable |
Full text not readStored summary read |
N43 · Long-term maintenance and effects of discontinuationWere lifelong maintenance/discontinuation effects mixed into the 90-day question?Extension boundary; required for maintenance/discontinuation claims |
The selected question is the 90-day Hb comparison; a lifelong monthly plan is not observation. Lifelong effects/maintenance after discontinuation are separate questions and were not required for this selected efficacy question. |
A long-term extension is not applicable to the selected 90-day efficacy question. Unverified long-term safety is retained separately. |
If a long-term maintenance/discontinuation question is added: actual follow-up, post-discontinuation Hb and exposure/denominators |
If a long-term extension is requested, obtain actual exposure/follow-up and arm-specific outcomes, rather than plans. |
| 44 |
Not applicable |
Full text not readStored summary read |
N44 · Extension to clinical eventsIs Hb an effect on fatigue, transfusion, death or daily functioning?Extension boundary; required for event/quality-of-life claims |
The selected outcome is the day-90 Hb(g/dL) laboratory surrogate; fatigue, transfusion, death and daily functioning are different questions. Event trials were not required for this Hb report, and Hb improvement was not extended into an effect on events. |
Extension to events is not applicable to the current numerical-outcome question. Neither absence nor presence of separate efficacy on events is established. |
If an event/quality-of-life claim is added: the relevant direct endpoint, time point/denominators and importance |
If extension to events is requested, separately obtain between-group data on the direct endpoint of interest. |
| 45 |
Not applicable |
Full text not readStored summary read |
N45 · Extension to other products and routesAre effects of tablets or other chemical forms/routes being compulsorily combined?Extension boundary; required for claims about other products/routes |
The current assessment concerns oral Dodex ampule+fruit juice versus the same cyano IM. Tablet, other chemical-form, sublingual, intravenous and intranasal results were not compulsorily combined. Gaps in the actual original product's batch/adherence were retained separately. |
Extensions outside the selected regimen are not applicable; this does not mean that all products/routes have the same effects. |
If a separate product/route claim is added: direct Hb comparison for that product, population and regimen |
If a separate regimen question is authorized, first fix the direct Hb criteria for each identity/route. |
| 46 |
Partly verified |
Full text not readStored summary read |
N46 · ID and publication metadataAre original ID/code and deployment expressions being read as the publication status of this review?Required (selected day-90 Hb comparison) |
The KO summary's ID/URL/semantic-code needs_id_assignment and the empty permanent_semantic_code/status coexist with general permanent/classification/semantic codes marked filled/assigned. initial_current_value_not_deployed, server_writefalse, server_deployedtrue, historical deployed_at and original final_url were also preserved. Public deployments of this local sheet total 0. |
Original identity/deployment expressions are preserved, but authority precedence and corrections to actual original publication status were not established within this scope. |
KO needs_id_assignment, null semantic, original automatic codes/assigned, server_deployed/not-deployed expressions and original URLs/dates |
If an identity/deployment correction is separately authorized, record the complete original, authority/decision and before/after values as an event. |
| 47 |
Met |
Full text not readStored summary read |
N47 · Updates and traceabilityAre there update rules that preserve original text, criteria and opposing values?Required (selected day-90 Hb comparison) |
Preserve the original revision_history and update leads concerning PDFs/plans, adjusted/change Hb, arm-specific denominators/rescue treatment, direct trials, funding/corrections and ID. Link the criteria frozen beforehand and observations/pointers, SHA and dates to each row; the original C46/Caution, opposing values and materials were not overwritten. |
Verification of the linkage criteria for traceability/update rules; not certification of completion of a new-evidence/correction event or of public publication. |
Original revision triggers, cutoff/actual review dates, prior freezing of criteria, exact values/pointers/SHA and before/after events/versions |
If authorized original PDFs, plans, direct trials, funding information or corrections arrive, review them while preserving a separate event, criteria version and before/after values. |
