Oral vitamin B6-only tablets (exact vitamer and salt unverified in the main trial) × Reduction of overall symptom severity in diagnosed PMS

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	Met	Full text not readStored summary read	N01 · Comparison of overall PMS symptomsWhich population, intervention, comparator, and endpoint define the distinct claim?Required	The original claim is “reduction of overall symptom severity in diagnosed PMS.” Oral B6-only tablets are compared with placebo in nonpregnant adults; PMDD, pregnancy nausea, and individual symptoms are not the direct claim. S02 S03	The scope and identity conditions are met. This does not mean that symptom improvement or the efficacy of a particular dose has been established.	Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint	Compare the current manuscript with each trial's population, intervention, comparator, and endpoint, and record the reason for a change only if a boundary has changed.
2	Partly verified	Full text not readStored summary read	N02 · Comparison of overall PMS symptomsAre the prospectively confirmed PMS population, modern diagnostic assessment, and differentiation from PMDD verified?Required	The main trial involved nonpregnant adults aged 18–45 and used prospective diaries over two diagnostic cycles. Deficiency status, detailed differentiation from PMDD, and modern diagnostic adjudication remain unverified. S02 S03	The diaries and age range are preserved, but the detailed diagnosis and baseline status have not all been verified.	Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status	First compare the diagnostic procedures across trials, then examine comparative records for PMS populations confirmed using the same definition.
3	Met	Full text not readStored summary read	N03 · Comparison of overall PMS symptomsIs the main trial's B6-only arm distinguished from the Hypericum and placebo arms?Required	S03 has separate parallel arms for B6 alone, Hypericum, and placebo. The current comparison uses only B6 and placebo and does not add the effect of Hypericum. S03	The arm composition and attribution of the selected comparison are preserved. The conditions for verifying allocation concealment and dose have not thereby also been met.	Original records of each arm's intervention list, regimen, and comparator composition	Check the interventions table by arm and classify monotherapy, combination therapy, and comparisons with other ingredients separately.
4	Unverified	Full text not readStored summary read	N04 · Comparison of overall PMS symptomsAre the vitamer and salt of B6 in the key trials verified?Required	The exact vitamer and salt in the key trials remain unverified. The manuscript states that B6 is not the name of a single molecule and that pyridoxine, pyridoxal, and PLP were not treated as identical. S02 S03 S15	General ingredient descriptions do not establish the identity of the actual trial product.	Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials	Cross-check the original trial's product identity records, and examine records for other vitamers as distinct exposures.
5	Partly verified	Full text not readStored summary read	N05 · Comparison of overall PMS symptomsAre details of the actual tablets, such as brand, origin, batch, and release form, verified?Required	The route is oral and the formulation is a tablet. Manufacturing origin, brand, crystal form, release form, and batch remain unverified or inconsistently described. S02 S03	Only the route and broad formulation have been verified; detailed product equivalence has not been established.	Manufacturing, product, batch, and release-form specifications for the administered tablets	Obtain trial-product documents to examine differences between formulations; do not substitute another commercial product.
6	Conflicting records	Full text not readStored summary read	N06 · Comparison of overall PMS symptomsAre the main trial's tablet strength and total daily dose consistently verified?Required	The main trial's tablet-strength descriptions conflict, leaving the total daily dose unverified. The currently retained archived summary preserves the fact of the conflict, but does not contain the specific conflicting tablet-strength numbers or original statements. S03	Consistency of the actual daily dose remains unresolved. Successfully recording the conflict is distinguished from verifying the exposure.	Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose	Compare the original dosing documents and revision history to verify a consistent exposure record, without calculating a new dose.
7	Not reported	Full text not readStored summary read	N07 · Comparison of overall PMS symptomsIs the supportive trial's daily B6 dose verified separately from the magnesium dose of 250 mg?Required	The retained S02 content explicitly states that the B6 dose could not be verified in the report. 250 mg refers to magnesium, not the daily dose in the B6-only arm. S02	The dose is described as not reported only within the supportive trial report content obtained at the time. This is not the result of a new check of the entire full text.	S02 records of the B6 dosing regimen and product, and the original dose statement	Compare the regimens by arm in S02 and extract the magnesium and B6 values separately.
8	Partly verified	Full text not readStored summary read	N08 · Comparison of overall PMS symptomsAre the diagnostic and treatment cycles and information on actual administration and adherence verified?Required	The main trial is preserved as 2 diagnostic recording cycles followed by 2 treatment cycles, with administration throughout the cycle. Actual adherence and arm-specific discontinuation and dosing changes remain unverified. S03	A nominal cycle schedule is available, but actual exposure received and adherence have not all been verified.	Cycle-specific records of administration, adherence, discontinuation, and rescue treatment	Compare the cycle schedule with actual administration records and examine deviations in relation to the actual effect of interest.
9	Unverified	Full text not readStored summary read	N09 · Comparison of overall PMS symptomsIs there direct evidence of sustained effects and long-term outcomes after treatment ends?Supplementary; required for a claim of sustained effects	The current manuscript leaves sustained long-term effects unverified. It does not claim that effects persisting after discontinuation have been verified from the two-treatment-cycle comparison alone. S02 S03	The currently archived material contains no direct estimate of sustained effects or follow-up information.	Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale	Define sustained effects as a separate question and examine comparative follow-up records after discontinuation.
10	Partly verified	Full text not readStored summary read	N10 · Comparison of overall PMS symptomsIs the actual comparison in terms of placebo, common drug regimens, and concomitant treatments verified?Required	The main trial's placebo is preserved as lactose and cellulose. The fixed common drug regimen and arm-specific concomitant and rescue treatments remain unverified. S03	Placebo composition has been verified, but the influence of other treatments and equivalence of background treatment have not all been verified.	Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes	Cross-check the actual comparator composition and background treatment to examine attribution of intervention differences.
11	Partly verified	Full text not readStored summary read	N11 · Comparison of overall PMS symptomsAre the allocation process, allocation concealment, and baseline balance verified?Required	The main trial is preserved as a parallel-group design, and baseline total scores are also available. Unverified allocation concealment or registration was not asserted to be actual absence; detailed allocation and analysis flow remain unverified. S03	Some design and score information is available, but the sequence, concealment, and overall baseline balance could not all be verified.	Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records	Compare the original methods and allocation records with baseline characteristics relevant to the outcome, and record what was actually verified.
12	Unverified	Full text not readStored summary read	N12 · Comparison of overall PMS symptomsAre blinding and collection procedures by group verified for the subjective diary assessment?Required	The currently archived material identifies a 12-symptom diary endpoint but does not contain specific details of how blinding was implemented or how diaries were collected by group. S03	Details of the measurement procedures cannot be verified within the summaries and structure currently saved.	Diary collection manual, blinding, assessment, and measurement schedules by group	Compare the methods section with the diary procedures and review the actual collection limitations for the subjective endpoint.
13	Partly verified	Full text not readStored summary read	N13 · Comparison of overall PMS symptomsAre the definition, direction, and aggregation range of the total 12-symptom diary score verified?Required	The main trial uses the total score of a 12-symptom diary, with lower scores indicating better outcomes. Total-score normalization and aggregation range remain unverified, and the manuscript does not call the older scale DRSP. S03	The composition and direction are preserved, but a reproducible definition of the total-score calculation remains incomplete.	Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials	Compare the original score definitions and distinguish the total score from subdomains and other scales.
14	Unverified	Full text not readStored summary read	N14 · Comparison of overall PMS symptomsCan the total-score calculation and normalization be verified reproducibly?Required	The original B2 rationale identifies a reporting and measurement problem: the explanation of total-score calculation and normalization is insufficiently reproducible. The currently archived summary does not contain the calculation formula. S03	The process used to generate the score cannot be reproduced within the currently preserved material.	Raw symptom scores, calculation formula, and rules for missing data and normalization	Compare the score-calculation documentation with the original table to review interpretability, without calculating a new score.
15	Unverified	Full text not readStored summary read	N15 · Comparison of overall PMS symptomsWere the primary-endpoint hierarchy, timing, and analysis plan specified in advance?Required	The registered hierarchy of the main trial's total score remains unverified. S02 has the identifier IRCT201106216854N1, but registration details, history, and whether registration was prospective could not be verified. S02 S03 S18	The existence of an identifier alone cannot verify agreement between the prospective plan and the actual report.	Dated registration, protocol, and analysis plan, and the results table for the overall endpoint	Compare plan versions and dates with the actual overall endpoint and analysis, and record what remains unchecked.
16	Conflicting records	Full text not readStored summary read	N16 · Comparison of overall PMS symptomsCan the flow of recruited, allocated, and analysed participants in the main trial be verified consistently?Required	The table analysis headers show B6 78 participants and placebo 78 participants. The manuscript states that internally inconsistent participant accounting across the abstract, methods, and tables makes a coherent analysis-population check difficult. Detailed recruitment and allocation counts are absent from the current summary. S03	The actual inconsistency in denominator flow remains unresolved, and the table denominators are not transferred to other stages.	Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group	Link each stage-specific and endpoint-specific denominator to its original location to check consistency only, without creating new participant totals.
17	Met	Full text not readStored summary read	N17 · Comparison of overall PMS symptomsDo the baseline and end-of-treatment means, SDs, and denominators in the main trial table belong to the specified total score?Required	The preserved table shows B6 33.93(SD 6.95)→20.92(SD 5.26), placebo 33.86(SD 6.16)→23.90(SD 6.00), with analysis headers of 78 participants per group. All are study-specific total scores. S03	The types, endpoints, and table-denominator attribution of the currently preserved numbers have been verified. This does not mean that the original full text was newly checked or that allocation flow was resolved.	Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers	Check the original locations of numbers, dispersion, and denominators, and preserve both the prior and revised values if corrections are made.
18	Met	Full text not readStored summary read	N18 · Comparison of overall PMS symptomsAre the preserved arithmetic change contrast and end-of-treatment difference distinguished from the formal adjusted effect?Required	In the manuscript, -3.05 points is the historical arithmetic change contrast derived from reported means, and -2.98 points is the end-of-treatment difference. These are not a formal adjusted change contrast or its confidence interval, and they were not recalculated in this review. S03	The type of historical arithmetic and its boundary with the formal estimator have been verified. This does not mean that the conditions for causal effect or precision have been met.	Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis	Perform only a traceability review comparing historical calculations with formal results, without producing new arithmetic values or CIs.
19	Unverified	Full text not readStored summary read	N19 · Comparison of overall PMS symptomsAre the formal between-group change contrast, adjustment method, and confidence interval verified?Required	Formal change-contrast confidence intervals remain unverified for the main and supportive trials. The manuscript retains the limitations that ANCOVA was not reported and correlations or variances were not estimated. S02 S03	The formal change-contrast analysis and its interval cannot be verified within the currently preserved material.	Original change-contrast analysis results, model, analysis population, variance, and CI	Compare the original results and analysis plan to verify the reported interval for the same estimator, without calculating a new interval.
20	Unverified	Full text not readStored summary read	N20 · Comparison of overall PMS symptomsIs the B6-placebo between-group test of change verified separately from within-group tests and the overall three-group test?Required	The manuscript states that within-group significance or the overall three-group test result was not substituted for the exact B6-placebo test of the change contrast. The currently archived summary does not contain the specific P value of that original test. S03	The limitations on test attribution have been preserved, but the exact test of change between the two groups and the handling of multiplicity remain unverified.	Original tests, post hoc contrasts, handling of multiplicity, and analysis plan	Identify the comparisons in the original test table and review within-group tests, the overall test, and the test of the two selected groups separately.
21	Unverified	Full text not readStored summary read	N21 · Comparison of overall PMS symptomsAre the analysis population, missing data, attrition, and definition of the effect of interest verified?Required	Detailed allocation and analysis flow remain unverified, and the main trial's table headers conflict with the overall participant-count description. In the supportive trial, completion counts and endpoint-specific analysis denominators may differ, so they are kept separate. S02 S03	Direct specifications of the effect of interest and missing-data handling could not be verified in the current summary.	Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications	Compare the analysis plan and flow diagram with the result denominators to distinguish the effect being estimated.
22	Partly verified	Full text not readStored summary read	N22 · Comparison of overall PMS symptomsAre the supportive trial's allocation, completion, and endpoint denominators and its 30-symptom results distinguished?Required	S02 allocated 42 participants per group; completers were B6 36 and placebo 37. The 30-symptom diary values B6 36.51→22.84 and placebo 35.80→28.41, and the historical arithmetic contrast of -6.28 points, are preserved, but endpoint-specific analysis denominators and the between-group change CI remain unverified. S02	Allocation and completion counts and scores are available, but endpoint denominators, variance, and formal intervals could not be established.	S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results	Compare the original tables with allocation, completion, and analysis kept as separate stages, without recalculating the currently preserved historical arithmetic.
23	Unverified	Full text not readStored summary read	N23 · Comparison of overall PMS symptomsIs there evidence supporting conversion of the 12-symptom and 30-symptom scales for comparison in the same effect units?Required	The main trial uses a 12-symptom diary, and the supportive trial uses a separate 30-symptom diary. The manuscript does not combine -3.05 points and -6.28 points and provides no evidence supporting conversion to a common scale. S02 S03	The fact that the scales differ has been verified, but comparability in the same clinical units remains unverified.	The two original scales, score ranges, validation, and evidence for the validity of conversion	Compare results separately by scale, and do not combine them into a common effect without validated evidence supporting conversion.
24	Partly verified	Full text not readStored summary read	N24 · Comparison of overall PMS symptomsHave the original Results location, scale, denominators, and dispersion for the carried-forward 80 mg/day values been recovered?Required	S06 preserves 80 mg/day, B6 -1.80 and placebo -0.93, an initial sample of 160 with 94 analysed, and the historical arithmetic change contrast of -0.87 points. The exact original Results location, scale, dispersion, and denominators by stage and arm remain unrecovered; these values were not used for grading or independent replication. S06	The carried-forward values and their limitations were preserved, but direct traceability to the original results and the analysis details could not be verified.	The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record	First review the provenance of the existing numbers, and do not integrate them quantitatively before their identity and scope are recovered.
25	Met	Full text not readStored summary read	N25 · Comparison of overall PMS symptomsIs the 2020 correction distinguished as an authorship change, an efficacy-number correction, or a retraction?Required	S07 is a 2020 correction adding the omitted author Shahnaz Babayanzad Ahari. It was not described as an efficacy-number correction or a retraction, and it belongs to the same trial publication family as S06. S06 S07	The correction type and trial relationship were distinguished in the retained record. The external full correction text has not been newly read in this review.	The changes and author list in the correction document, and its link to the original article	Compare only the items changed by correction or retraction documents; review changes to the original numbers only when separately verified.
26	Partly verified	Full text not readStored summary read	N26 · Comparison of overall PMS symptomsDo the 1999 review's 9 trials and 940 participants all represent the same eligible comparison?Required	The review's 9 trials and 940 participants include multivitamin trials and trials assessing mastalgia alone. They do not all represent the same comparison of overall PMS symptoms with B6 monotherapy, and they are not added up as independent studies in the current table. S01	The heterogeneous inclusion scope was identified, but detailed eligibility and cohort relationships could not be established for every trial.	S01's included-trial table, interventions, populations, endpoints, and links to original reports	Compare the included trials against each question, and do not use review totals as the number of study families or the denominator for the current effect.
27	Partly verified	Full text not readStored summary read	N27 · Comparison of overall PMS symptomsCan the definition, denominator, and comparator represented by the review's improvement OR 2.15 be verified?Required	For the B6-only subgroup, an improvement OR of 2.15 (CI 1.79–2.59) is retained. It is not a percentage reduction in the overall symptom score or an individual's probability of improvement. The currently archived summary does not contain a table of improvement classifications or subgroup events and denominators. S01	The measure, subgroup, and interval are available, but traceability of the specific improvement definition and event denominators remains incomplete.	S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table	Link the review's categorical results to the original table and review them separately from score results, without recalculating effects.
28	Partly verified	Full text not readStored summary read	N28 · Comparison of overall PMS symptomsAre reports from the same trial, protocols, and possible cohort overlaps identified?Required	S11 is grouped as an earlier partial report of S03, and S21 as the protocol for S08. Possible cohort overlap between S19 and S02 remains unverified, and it is not counted as independent replication of B6 monotherapy. S02 S03 S08 S11 S19 S21	The two family links are present, but the actual cohort relationship of S19/S02 and the total unique participant count remain unverified.	A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials	Link reports to trial families, distinguish confirmed, possible, and unknown relationships, and leave unverified unique participant counts blank.
29	Partly verified	Full text not readStored summary read	N29 · Comparison of overall PMS symptomsAre the boundaries between overall results that are not favorable, emotional-domain results, and other interventions identified?Required	Doll's emotional-domain signal is not transferred to overall improvement. Kendall's original overall mean and CI remain unverified. S08 involves an active comparator and inclusion of riboflavin; S09 concerns anxiety with a combination; S19 is a combination study; and S20 has no B6 arm. These are kept separate from the direct overall effect. S04 S05 S08 S09 S19 S20	Contrary and scope-limited materials were retained, but the complete original overall results and detailed comparisons in older studies have not all been verified.	Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators	Compare favorable, no-difference, and unfavorable results as materials addressing the same question, while separating results for other endpoints or interventions.
30	Partly verified	Full text not readStored summary read	N30 · Comparison of overall PMS symptomsAre research funding, product supply, and conflict-of-interest declarations verified separately from independent funding?Required; interpretation of independence	S03 distinguishes the authors' declaration of no COI from the unverified specific funding and B6 supplier. In S02, supply of coded tablets by the university pharmacy was verified, but funding and author COI remain unverified. Other trials likewise retain their unresolved details within the available material scope. S02 S03 S04 S05 S06	Some supply and declaration details are available, but independent funding and all supply and employment relationships could not be established.	Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations	Compare declarations separately with actual funding and supply materials, and record the limits on interpreting independence.
31	Unverified	Full text not readStored summary read	N31 · Comparison of overall PMS symptomsAre adverse-event collection, denominators, and follow-up verified for the same PMS population and exposure?Supplementary; required for interpreting safety	The original safety explanation states that the absence of reports of serious adverse events in short trials does not establish long-term neurological safety. The currently retained archived summary does not contain complete AE collection tables, denominators, or discontinuation results for each PMS comparison. S02 S03 S12 S13 S14 S16	A complete harm comparison for the same population, actual dose, and duration could not be verified.	Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials	Compare efficacy and harm outcomes separately, and review follow-up and collection methods suited to neurological outcomes.
32	Partly verified	Full text not readStored summary read	N32 · Comparison of overall PMS symptomsAre general B6 neuropathy warnings distinguished from risk estimates in PMS trials?Supplementary; required for extrapolating harms	The retained TGA account records neuropathy reports even below 50 mg/day and warns about cumulative intake and potentially irreversible injury. This does not newly establish the incidence in PMS trials or comparative risk by specific vitamer or product. S12 S13 S14 S16	General safety context is available, but there is no exposure, denominator, and risk comparison matching the PMS trials.	Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up	Review general regulatory and safety-signal materials separately from direct comparative harm materials, and do not calculate new thresholds or risks.
33	Met	Full text not readStored summary read	N33 · Comparison of overall PMS symptomsAre the EFSA upper limit and Australia's future regulation distinguished from treatment doses and current regulations?Supplementary; indication of regulatory and safety scope	The original cutoff is 2026-09-15. EFSA's adult 12 mg/day is an upper limit for chronic total intake; TGA's pharmacist-only change for above 50 mg~up to 200 mg/day is retained as scheduled to take effect on 2027-06-01. These are not treatment doses or current evidence of efficacy. S12 S14	Only the meaning and date boundaries of the retained regulatory and safety record were checked. This status does not newly certify current law or individual safety.	The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date	Within an authorized update scope, compare document editions and effective dates, and keep them separate from treatment doses and biological thresholds.
34	Unverified	Full text not readStored summary read	N34 · Comparison of overall PMS symptomsAre statistical magnitude, clinical importance, and other clinical questions kept separate?Required	The historical end-of-treatment Hedges g=-0.53 is a statistical-magnitude classification under the original scoring rubric, not a validated between-group MCID. Clinical importance and sustained benefit remain unverified, and this is not a verdict on PMDD or pregnancy nausea. S02 S03	The statistical value was preserved, but there is no validated clinical-importance criterion for this scale or direct evidence for events or other populations.	Materials on a validated MCID, importance to patients, and applicability for the overall scale in question	Compare evidence on importance to patients and scale validation against the results, without inventing arbitrary thresholds or success probabilities.
35	Met	Full text not readStored summary read	N35 · Comparison of overall PMS symptomsIs actual reading of local summaries distinguished from past access, external materials not read in this review, and the associated dates?Required	This review read the currently retained KO/EN manuscripts, 9 evidence entries, 21 bibliographic entries, and metadata. The original verified_date is 2026-09-15, and there is no actual-access-date key for each citation. Each material's access date is blank; the original review date is separate. External originals, separate indexes/ZIP files, and 127 were not read in this review. S01 S02 S03 S04 S05 S06 S07 S08 S09 S10 S11 S12 S13 S14 S15 S16 S17 S18 S19 S20 S21	This condition records the boundary between actual local actions and historical declarations. It does not directly certify the current contents of external materials.	Records of actual access, acquisition, and reading events, with material-specific dates and original locations	Review access events separately for each material, and add current actions and dates only when new reading is authorized.
36	Met	Full text not readStored summary read	N36 · Comparison of overall PMS symptomsAre the original C·50 assessment and the different verdict and policy of historical composite record 127 kept separate from current condition statuses?Required	The judgment in the current manuscript is C·50, with axes B/P/R1/I1/E+/B2/CX. The combined PMS/pregnancy-nausea record in 127 and its B·60 are related history and have not been repurposed for the current PMS-only claim. Preserve the numbers and original metadata of the current original judgment unchanged.	The separation of current/historical judgments and the rule that they remain unchanged were verified. C·50 is not used as evidence that individual conditions are met.	Current judgment, relationships to related records, original axes and version metadata	When making a correction, preserve the original event, before-and-after values and version, and distinguish revision of the conditions from a change in the clinical judgment as separate tasks.
37	Met	Full text not readStored summary read	N37 · Comparison of overall PMS symptomsAre statements of insufficiency or uncertainty linked to the scope of preservation, reference date and conditions for updating?Required	Record from the preservation-table review dated 2026-10-05: The original evidence reference date is 2026-09-15, and the review date for that work was 2026-10-05. Update conditions include dose, vitamer, hierarchy, scale, denominators, intervals, corrections, safety and recovery of the original location for the 80 mg/day record. The existing ZIP/calculation records were references only; no new search or effect calculation was performed.	The record of the scope verified and the update conditions was checked. This does not certify the completeness of the literature or the presence or absence of an effect.	Dates, the actual preserved records of search/selection/calculation, and the original location of each update event	When new materials are permitted and become available, compare their identity, scope and version, and review only the observations and status of the relevant conditions again.

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37 itemsWhat the statuses mean

Assessment scope

Stored-material review date: 2026-10-05
Original evidence date: 2026-09-15
Scope actually checked: Archived Korean and English manuscripts and case-specific condition and application records. Full papers, supplements, registrations, plans and original data were not read.
What the dates mean: This is the date the archived material was checked, not the date of a search for the latest clinical literature.
Population: Nonpregnant adults with PMS; main trial ages 18–45 with prospective symptom diaries; deficiency status and detailed differentiation from PMDD unverified
Ingredient, formulation and route: Vitamin B6 alone; vitamer and salt unverified in the main trial · Oral tablets; brand, crystal form, release form, and batch unverified · Oral
Dose: Daily total dose unverified: conflicting descriptions of tablet strength in the main trial; B6 dose not reported in the supportive trial
Comparator: Placebo; lactose and cellulose in the main trial; fixed common drug regimen unverified
Measured outcome: Main trial total score from a 12-symptom diary; registered outcome hierarchy and aggregation range unverified; lower is better
Duration: 2 diagnostic recording cycles followed by 2 treatment cycles; administration throughout the cycle
Questions outside this scope: PMDD, pregnancy nausea, individual emotional/anxiety symptoms, mastalgia, combination products, active comparators, and other scales/distinct studies are not combined as the same effect on the current overall score. OR, end-of-treatment difference, arithmetic change contrast, the carried-forward 80 mg record, and MCID are each kept distinct.

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.

S01 · Wyatt et al. 1999. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review

Source

Material type: Full HTML text of the original review article
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: This is an older review with mixed interventions and endpoints. It is not counted as a new independent trial.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full HTML text of the original review article	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. This is an older review with mixed interventions and endpoints. It is not counted as a new independent trial. Original location: Abstract; Table 1; vitamin B6 alone subgroup; Discussion. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S02 · Ebrahimi et al. 2012. Effects of Magnesium and Vitamin B6 on the Severity of Premenstrual Syndrome Symptoms

Source

Material type: PMC link to the original article (distinct from the historical indexed extract)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Actual comparison/role: Separate magnesium, B6-only and placebo arms; B6 dose not reported. Denominator: Allocated 42 per group; completed B6 36 and placebo 37; endpoint denominator unverified. Endpoint: Overall score from a separate 30-symptom diary; a different scale from the main trial. Result: B6 36.51→22.84, placebo 35.80→28.41; arithmetic change contrast -6.28 points; between-group change CI unverified. Funding: Coded tablets supplied by the university pharmacy verified; funding and author COI unverified. Limitations: Supportive evidence; not pooled with a different scale. Allocated 42 per group; completed B6 36/placebo 37; endpoint analysis denominator unverified. 250 mg refers to magnesium, and the B6 dose was not reported. The historical arithmetic -6.28 points is not pooled with the main 12-symptom scale.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PMC link to the original article (distinct from the historical indexed extract)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_full_text. The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Original location: Methods; Results; Table 1; article registration header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Indexed full-text extract at the time of preservation (separate copy not read in this task)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_full_text. Contextual level recorded for the containing document: indexed_full_text. The full text was read through a search index, and direct repeat access was blocked. B6 dose unverified; 250 mg refers to magnesium. Original location: Methods; Results; Table 1; article registration header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S03 · Ghazanfarpour et al. 2017. Hypericum perforutum and Vitamin B6 as a Treatment for Premenstrual Syndrome

Source

Material type: Full HTML text of the original article on the publisher site
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Actual comparison/role: Parallel B6-only, Hypericum and placebo arms; only B6 and placebo are used for this effect. Denominator: Table analysis headers B6 78 and placebo 78; overall recruitment/allocation descriptions conflict. Endpoint: Overall total of the 12-symptom diary; lower is better; total-score normalization unverified. Result: Baseline→end B6 33.93→20.92, placebo 33.86→23.90; arithmetic change contrast -3.05 points; formal change-contrast CI unverified. Funding: Specific funding and B6 product supplier unverified; the authors’ no-conflict declaration is separate from proof of independent funding. Limitations: Main evidence; limitations in bias and measurement reporting. The preserved table has B6 33.93(SD 6.95)→20.92(SD 5.26), placebo 33.86(SD 6.16)→23.90(SD 6.00), with 78 per group. The historical arithmetic change contrast -3.05 points, end-of-treatment difference -2.98 points and end-of-treatment Hedges g=-0.53 are not an official adjusted change contrast or MCID. The original test P, detailed participant counts and tablet-strength wording are absent from the currently archived summary.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full HTML text of the original article on the publisher site	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Original location: PDF pp.1–3: Methods, Results, Table 1 Total row and footnote, Table 2; p.5 Footnotes/ref.8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Full PDF of the original article (exact PDF URL currently unverified)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Records of HTML/PDF acquisition and visual table checking were reused. B6 is a separate arm from Hypericum. Original location: PDF pp.1–3: Methods, Results, Table 1 Total row and footnote, Table 2; p.5 Footnotes/ref.8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S04 · Doll, Brown, Thurston and Vessey 1989. Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial

Source

Material type: PubMed abstract
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Abstract-level access. The original overall-score tables and paired variance could not be verified. Actual comparison/role: Pyridoxine 50 mg/day versus placebo; crossover design. Denominator: 63 entered; the full 7 months were completed by 32 participants; endpoint-specific denominators unverified. Endpoint: A 9-symptom diary; distinguish the emotional-domain signal from overall PMS. Result: The emotional-subdomain result is not repurposed as overall symptom improvement. Funding: Funding and COI unverified in the accessed abstract. Limitations: Qualitative evidence with a limited scope.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed abstract	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: abstract. Contextual level recorded for the containing document: abstract. Abstract-level access. The original overall-score tables and paired variance could not be verified. Original location: Abstract: design, entry/completion, emotional-symptom findings. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Full text of the original article (exact URL and historical full-text access currently unverified)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: abstract. Abstract-level access. The original overall-score tables and paired variance could not be verified. Original location: Abstract: design, entry/completion, emotional-symptom findings. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S05 · Kendall and Schnurr 1987. The effects of vitamin B6 supplementation on premenstrual symptoms

Source

Material type: PubMed bibliographic/abstract link (distinct from the historical index)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Actual comparison/role: Pyridoxine 150 mg/day versus placebo. Denominator: Review record of 55 completers; original endpoint denominator unverified. Endpoint: Mixed subdomains; original overall-score mean unverified. Result: The overall symptom mean and confidence interval could not be verified. Funding: Unverified; independence of the study is not assumed. Limitations: Secondary (2nd) extraction and limited qualitative material.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic/abstract link (distinct from the historical index)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_abstract. Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Original location: Indexed abstract; S01 Table 1 and S10 Table 1 for secondary details. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Indexed abstract/review extract at the time of preservation (separate copy not read in this task)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_abstract. Contextual level recorded for the containing document: indexed_abstract. Indexed abstract and secondary (2nd) extraction from reviews. The original overall-score mean is unverified. Original location: Indexed abstract; S01 Table 1 and S10 Table 1 for secondary details. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S06 · Kashanian et al. 2007. Pyridoxine (vitamin B6) therapy for premenstrual syndrome

Source

Material type: PubMed bibliographic link (original result location not recovered)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and an initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Actual comparison/role: Preserved record of pyridoxine 80 mg/day versus placebo; salt and exact formulation unverified. Denominator: Preserved record of an initial 160 with 94 analysed; stage-specific and per-arm denominators unverified. Endpoint: Values carried as overall PMS change; exact scale and original text location not recovered. Result: -1.80 versus -0.93 preserved, arithmetic difference -0.87; no SD/CI/p values invented. Funding: Funding, product supply and COI unverified; an author was added by correction in 2020. Limitations: Preservation of carried values only; not used for new original-source verification, grading or independent replication. The 80 mg/day, B6 -1.80 versus placebo -0.93, initial 160 with 94 analysed, and historical arithmetic -0.87 points are values carried in the request to resume the work. Per-arm denominators/dispersion/original Results location were not recovered, so these were not used as new verification, for grading or as replication.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic link (original result location not recovered)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Original location: Bibliographic record; secondary trial description in review literature. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Full text of the original article (exact original Results location and historical full-text access unverified)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Metadata-access records are distinguished from the numbers in the request to resume the work. The 80 mg/day, -1.80 versus -0.93, and initial 160 with 94 analysed were preserved but not used for grading because the original result location and dispersion were not recovered. Original location: Bibliographic record; secondary trial description in review literature. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S07 · Kashanian et al. 2020. Corrigendum to Pyridoxine (vitamin B6) therapy for premenstrual syndrome

Source

Material type: Link to the correction adding an author
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: This is a correction adding an author in 2020. It was not described as a numerical correction or a retraction.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Link to the correction adding an author	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. This is a correction adding an author in 2020. It was not described as a numerical correction or a retraction. Original location: Corrigendum text and corrected author list. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S08 · Retallick-Brown, Blampied and Rucklidge 2020. A Pilot Randomized Treatment-Controlled Trial Comparing Vitamin B6 with Broad-Spectrum Micronutrients for Premenstrual Syndrome

Source

Material type: PubMed bibliographic link (active comparator/composition cross-checked in a review)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: This used an active comparator, and the review describes inclusion of riboflavin. It is not a strict B6-only versus placebo comparison. Actual comparison/role: Broad-spectrum micronutrients versus a B6 comparator; the review also describes riboflavin. Denominator: Not used as a denominator for the present B6-only versus placebo effect. Endpoint: Do not mix modified DRSP with other scales or comparison specifications. Result: Excluded from the direct effect because there was no placebo and the strict monotherapy condition was not met. Funding: Original funding and COI unverified; no additional credit for independence. Limitations: Excluded evidence.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic link (active comparator/composition cross-checked in a review)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. This used an active comparator, and the review describes inclusion of riboflavin. It is not a strict B6-only versus placebo comparison. Original location: Bibliographic record; design and composition cross-checked in S10 Table 1. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S09 · De Souza et al. 2000. Magnesium plus vitamin B6 and anxiety-related premenstrual symptoms

Source

Material type: PubMed bibliographic link (combination-intervention anxiety result)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: The anxiety subdomain result for a combination intervention is not the overall PMS effect of B6 alone. Possible report overlap was handled conservatively. Actual comparison/role: Distinguish magnesium, B6, combination and placebo crossover data. Denominator: Not counted as a new denominator for the present overall-severity effect. Endpoint: The anxiety subdomain and overall severity are separate. Result: Do not repurpose the combination-intervention anxiety result as overall symptoms with B6 alone. Funding: Unverified. Limitations: Limited scope; excluded from the direct effect.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PubMed bibliographic link (combination-intervention anxiety result)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: metadata. Contextual level recorded for the containing document: metadata. The anxiety subdomain result for a combination intervention is not the overall PMS effect of B6 alone. Possible report overlap was handled conservatively. Original location: Bibliographic record; S01 and S10 trial tables for related crossover material. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S10 · Robinson et al. 2025 (online 2024). Effect of nutritional interventions on the psychological symptoms of premenstrual syndrome in women of reproductive age: a systematic review of randomized controlled trials

Source

Material type: Full HTML text of the original review article
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Used for identifying updates and cross-checking. Psychological symptoms and overall symptom severity are different endpoints.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full HTML text of the original review article	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Used for identifying updates and cross-checking. Psychological symptoms and overall symptom severity are different endpoints. Original location: Table 1, vitamin B6 rows; discussion and risk-of-bias sections. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S11 · Ghazanfarpour et al. 2011. Hypericum perforatum for the treatment of premenstrual syndrome

Source

Material type: DOI bibliographic link (original full text not historically acquired)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Explicitly identified as an earlier partial report of S03, so it belongs to the same trial family. The original full text was not acquired.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
DOI bibliographic link (original full text not historically acquired)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Explicitly identified as an earlier partial report of S03, so it belongs to the same trial family. The original full text was not acquired. Original location: S03 Methods statement and reference 8. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S12 · TGA 2026. Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)

Source

Material type: Full text of the official TGA webpage
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: The change to pharmacist-only status for above 50 mg~up to 200 mg/day was scheduled to take effect on 2027-06-01 and was not treated as a regulation in force at the reference date.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of the official TGA webpage	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. The change to pharmacist-only status for above 50 mg~up to 200 mg/day was scheduled to take effect on 2027-06-01 and was not treated as a regulation in force at the reference date. Original location: Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S13 · TGA 2026. Are you unknowingly taking too much vitamin B6?

Source

Material type: Full text of the official TGA webpage
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Official safety information on neuropathy and cumulative intake, not PMS efficacy evidence.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of the official TGA webpage	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Official safety information on neuropathy and cumulative intake, not PMS efficacy evidence. Original location: 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S14 · EFSA 2023. Scientific opinion on the tolerable upper intake level for vitamin B6

Source

Material type: EFSA official literature link (distinct from the linked Wiley full text)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
EFSA official literature link (distinct from the linked Wiley full text)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: full_text. The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose. Original location: Abstract; Conclusions, adult UL derivation. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Linked original Wiley full text (exact URL currently unverified)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. The upper intake level of 12 mg/day in the officially linked full text concerns chronic total intake, not a treatment dose. Original location: Abstract; Conclusions, adult UL derivation. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S15 · NIH ODS. Vitamin B6: Fact Sheet for Health Professionals

Source

Material type: NIH official full-webpage link (distinct from historical index/print access)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
NIH official full-webpage link (distinct from historical index/print access)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: indexed_text. Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial. Original location: Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.
Indexed/print content at the time of preservation (separate copy not read in this task)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: indexed_text. Contextual level recorded for the containing document: indexed_text. Direct-request errors occurred, so only content accessed through an index or print view was used. It does not establish the salt used in the trial. Original location: Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read. The direct URL of this physical material is not preserved. A bibliographic link is not substituted for a direct file URL.

S16 · MedlinePlus. Pyridoxine drug information

Source

Material type: Full text of the official MedlinePlus webpage
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Used to check medicines, supplements and special populations; no PMS efficacy recommendation was imported.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Full text of the official MedlinePlus webpage	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: full_text. Contextual level recorded for the containing document: full_text. Used to check medicines, supplements and special populations; no PMS efficacy recommendation was imported. Original location: Special precautions; side effects; revised 15 August 2017. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S17 · ACOG 2023. Management of Premenstrual Disorders, Clinical Practice Guideline No. 7

Source

Material type: ACOG guideline literature link (historical full-text access failed)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Full-text access to the guideline failed. Its recommendations were not used for efficacy grading. It is separate from pregnancy-nausea guidance.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
ACOG guideline literature link (historical full-text access failed)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. Full-text access to the guideline failed. Its recommendations were not used for efficacy grading. It is separate from pregnancy-nausea guidance. Original location: Bibliographic identity and official URL only. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S18 · IRCT201106216854N1 registration pointer

Source

Material type: WHO registration-record link (detailed history unverified)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: The registration identifier appears in the original article, but registry details, history and whether registration was prospective could not be verified.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
WHO registration-record link (detailed history unverified)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. The registration identifier appears in the original article, but registry details, history and whether registration was prospective could not be verified. Original location: Registration number in S02 article header. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S19 · Fathizadeh et al. 2010. Evaluating the effect of magnesium and magnesium plus vitamin B6 supplement on the severity of premenstrual syndrome

Source

Material type: PMC original-article link (historical verification was indexed bibliographic information)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Excluded because this was a combination trial. Possible overlap with S02 is unverified, and it was not counted as independent replication. Actual comparison/role: Comparisons such as magnesium versus magnesium+B6. Denominator: Not added as participants in an independent B6-only replication. Endpoint: Not an overall effect of B6 alone. Result: Excluded from the direct effect because this was a combination intervention. Funding: Unverified. Limitations: Excluded; overlap with S02 unverified.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
PMC original-article link (historical verification was indexed bibliographic information)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: metadata. Excluded because this was a combination trial. Possible overlap with S02 is unverified, and it was not counted as independent replication. Original location: Indexed title/metadata and related trial discussion. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S20 · 2025. Comparison of the Effects of Vitagnus, Soy, and Vitagnus-soy Capsules on the Severity of Premenstrual Syndrome

Source

Material type: Original-article PDF link (historical verification was the p.1 abstract section)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Excluded as a false-positive search result with no B6 intervention. Actual comparison/role: Vitagnus, soy and combination; no B6 arm. Denominator: Not counted as participants for a B6 effect. Endpoint: Not applicable to the present B6 endpoint. Result: Excluded as a wrong-intervention search result. Funding: No separate funding extraction was performed for this excluded study. Limitations: Excluded.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
Original-article PDF link (historical verification was the p.1 abstract section)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: Unverified. Contextual level recorded for the containing document: full_text. Excluded as a false-positive search result with no B6 intervention. Original location: PDF p.1 abstract visually checked. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

S21 · Retallick-Brown et al. 2016. Micronutrients for premenstrual symptoms: study protocol

Source

Material type: MDPI protocol link (historical direct 429 response/indexed information)
Materials actually read: The corresponding Korean and English summaries and bibliographic records in the archived manuscript were read. The linked external original materials have not been read in this task.
Findings recorded in the stored summary: Record at the time of preservation: Access was restricted, and this was grouped as the protocol for S08. It is not a separate trial or effect.
Record level: This is content recorded in the archived manuscript, not the result of a new comparison with the current external original materials.
Study overlap and independent replication: Link the original evidence families and explicitly stated same-trial/protocol relationships. Do not assign clinical trial families to reviews or general documents. Registry details and overlap between S19/S02 remain unverified.

Public availability, access and reading status by material
Material	Public availability	Access status	Actually read	Notes
MDPI protocol link (historical direct 429 response/indexed information)	Currently unverified	Not attempted this time	Not read	The historical access date of each material is unverified. The archived manuscript’s review date, 2026-09-15, is not this file’s access date. Historical access level recorded for this physical material: access_failed. Contextual level recorded for the containing document: access_failed. Access was restricted, and this was grouped as the protocol for S08. It is not a separate trial or effect. Original location: Indexed protocol information only. The historical access level is recorded only when access to this physical material is explicitly stated in the source. Access to separate links, original full texts, indexed/print extracts or the whole PDF is not automatically inherited from the containing document’s access level. The archived summary was read in this task; the external material was not attempted, acquired or read.

Report counts versus independent study counts

The 21 reports do not mean 21 independent trials. S03/S11 and S08/S21 each belong to the same family, while overlap between S19/S02 is unverified. The current counts of eligible unique trials, participants and independent replications were not newly calculated. TF-GHAZ (S03, S11): Parallel B6-only, Hypericum and placebo arms; only B6 and placebo are used for this effect · Main evidence; limitations in bias and measurement reporting / TF-EBRA (S02, S18): Separate magnesium, B6-only and placebo arms; B6 dose not reported · Supportive evidence; not pooled with a different scale / TF-DOLL (S04): Pyridoxine 50 mg/day versus placebo; crossover design · Qualitative evidence with a limited scope / TF-KENDALL (S05): Pyridoxine 150 mg/day versus placebo · Secondary (2nd) extraction and limited qualitative material / TF-KASH (S06, S07): Preserved record of pyridoxine 80 mg/day versus placebo; salt and exact formulation unverified · Preservation of carried values only; not used for new original-source verification, grading or independent replication / TF-RET (S08, S21): Broad-spectrum micronutrients versus a B6 comparator; the review also describes riboflavin · Excluded evidence / TF-DESOUZA (S09): Distinguish magnesium, B6, combination and placebo crossover data · Limited scope; excluded from the direct effect / TF-FATH (S19): Comparisons such as magnesium versus magnesium+B6 · Excluded; overlap with S02 unverified / TF-VITAGNUS (S20): Vitagnus, soy and combination; no B6 arm · Excluded

Review criteria

Version NGM-v3095-B6-MONOTHERAPY-PMS-GLOBAL-SEVERITY-1.0 · Criteria record date 2026-10-05. 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 · Which population, intervention, comparator, and endpoint define the distinct claim?

Required materials and conditions: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint
Conditions for verification: The current /ko/effect is linked to the boundaries of nonpregnant PMS, oral B6 monotherapy, placebo, and overall symptom score.
Requirement and applicability: Required
Application exceptions: Evidence for PMDD, individual emotional symptoms, mastalgia, or pregnancy nausea is not transferred to the current claim.
Why this condition is needed: The current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea.
Referenced methods: C01: question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C04: M03 §3.2.1; detailed population conditions are self-designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are self-designed. Reason for applying these to this overall PMS score comparison: the current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea. No formal RoB2/GRADE assessment or clinical certification was performed.

N02 · Are the prospectively confirmed PMS population, modern diagnostic assessment, and differentiation from PMDD verified?

Required materials and conditions: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status
Conditions for verification: The diagnostic cycles, participant ages and selection, differentiation from PMDD, and baseline nutritional status are linked to actual records.
Requirement and applicability: Required
Application exceptions: Unverified diagnostic details are not taken to mean that no PMS population exists or that treatment is ineffective for PMDD.
Why this condition is needed: Self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population. No formal RoB2/GRADE assessment or clinical certification was performed.

N03 · Is the main trial's B6-only arm distinguished from the Hypericum and placebo arms?

Required materials and conditions: Original records of each arm's intervention list, regimen, and comparator composition
Conditions for verification: The actual parallel-arm composition is distinguished from the B6-versus-placebo comparison to be used in this table.
Requirement and applicability: Required
Application exceptions: The use of Hypericum in another arm is not taken to imply concurrent administration in the B6-only arm.
Why this condition is needed: Reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E01: M08 §8.1–8.2.3; self-applied / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution. No formal RoB2/GRADE assessment or clinical certification was performed.

N04 · Are the vitamer and salt of B6 in the key trials verified?

Required materials and conditions: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials
Conditions for verification: Verify the vitamer and salt of the product actually administered using trial-specific documents or manufacturing records.
Requirement and applicability: Required
Application exceptions: The trial's salt is not filled in from common commercial products or general NIH descriptions.
Why this condition is needed: Pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures. No formal RoB2/GRADE assessment or clinical certification was performed.

N05 · Are details of the actual tablets, such as brand, origin, batch, and release form, verified?

Required materials and conditions: Manufacturing, product, batch, and release-form specifications for the administered tablets
Conditions for verification: Verify the oral route and actual product, batch, and release form, and distinguish the unverified dimensions.
Requirement and applicability: Required
Application exceptions: Unverified origin or brand is not converted into a finding that another product lacks efficacy.
Why this condition is needed: The fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: the fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions. No formal RoB2/GRADE assessment or clinical certification was performed.

N06 · Are the main trial's tablet strength and total daily dose consistently verified?

Required materials and conditions: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose
Conditions for verification: Tablet strength, number of tablets, frequency, total daily dose, and the basis for conversion are linked consistently.
Requirement and applicability: Required
Application exceptions: Do not reconstruct numbers absent from the conflicting original statements or use the study dose as dosing instructions.
Why this condition is needed: Conflicting descriptions of the study dose limit interpretation of the actual exposure and dose.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: conflicting descriptions of the study dose limit interpretation of the actual exposure and dose. No formal RoB2/GRADE assessment or clinical certification was performed.

N07 · Is the supportive trial's daily B6 dose verified separately from the magnesium dose of 250 mg?

Required materials and conditions: S02 records of the B6 dosing regimen and product, and the original dose statement
Conditions for verification: In S02, verify the actual B6 amount at its original location, and keep it separate from the magnesium dose.
Requirement and applicability: Required
Application exceptions: 250 mg is not relabeled as a B6 value. The absence of reporting is not generalized to the entire full text, which was not read in this review.
Why this condition is needed: Transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure. No formal RoB2/GRADE assessment or clinical certification was performed.

N08 · Are the diagnostic and treatment cycles and information on actual administration and adherence verified?

Required materials and conditions: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment
Conditions for verification: Verify the two diagnostic cycles, two treatment cycles, administration throughout the cycle, and actual adherence and discontinuation as distinct matters.
Requirement and applicability: Required
Application exceptions: The two cycles are not converted into a fixed number of days or an optimal treatment duration.
Why this condition is needed: Diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence. No formal RoB2/GRADE assessment or clinical certification was performed.

N09 · Is there direct evidence of sustained effects and long-term outcomes after treatment ends?

Required materials and conditions: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale
Conditions for verification: Follow-up time points, post-discontinuation outcomes, and sustained effects are linked through separate direct evidence.
Requirement and applicability: Supplementary; required for a claim of sustained effects
Application exceptions: A long-term trial is not made mandatory for every study addressing the current narrow question of two cycles.
Why this condition is needed: Needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects.
Referenced methods: E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying this to this overall PMS score comparison: this is needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects. No formal RoB2/GRADE assessment or clinical certification was performed.

N10 · Is the actual comparison in terms of placebo, common drug regimens, and concomitant treatments verified?

Required materials and conditions: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes
Conditions for verification: Distinguish placebo composition and common treatment from arm-specific concomitant treatments and changes using actual records.
Requirement and applicability: Required
Application exceptions: Do not assume that all changes in both arms are identical or fill an unverified field with an assertion of no concomitant treatment.
Why this condition is needed: Needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: this is needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy. No formal RoB2/GRADE assessment or clinical certification was performed.

N11 · Are the allocation process, allocation concealment, and baseline balance verified?

Required materials and conditions: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records
Conditions for verification: The random sequence, concealment, selection stages, and baseline balance relevant to the outcome are linked to their actual source locations.
Requirement and applicability: Required
Application exceptions: Do not assert that unverified allocation concealment was actually absent.
Why this condition is needed: An RCT label alone does not establish that errors in the allocation process or confounding have been resolved.
Referenced methods: E01: M08 §8.1–8.2.3; custom application. Reason for applying this to the PMS total-score comparison: an RCT label alone does not establish that allocation errors or confounding have been resolved. No formal RoB2/GRADE/clinical certification was performed.

N12 · Are blinding and collection procedures by group verified for the subjective diary assessment?

Required materials and conditions: Diary collection manual, blinding, assessment, and measurement schedules by group
Conditions for verification: Verify the actual procedures for diary completion, collection timing, assessors, and blinding by group.
Requirement and applicability: Required
Application exceptions: Do not use unverified blinding information to establish blinding failure or the magnitude of bias.
Why this condition is needed: For patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score.
Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: for patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score. No formal RoB2/GRADE/clinical certification was performed.

N13 · Are the definition, direction, and aggregation range of the total 12-symptom diary score verified?

Required materials and conditions: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials
Conditions for verification: Verify the direction, composition, aggregation range, and scale name of the 12-symptom total score against the actual material.
Requirement and applicability: Required
Application exceptions: Do not call the older diary DRSP or transfer significance in a subdomain to the overall endpoint.
Why this condition is needed: This is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score. No formal RoB2/GRADE/clinical certification was performed.

N14 · Can the total-score calculation and normalization be verified reproducibly?

Required materials and conditions: Raw symptom scores, calculation formula, and rules for missing data and normalization
Conditions for verification: The calculation, missing-data handling, and normalization methods from individual symptom records through to the total score are verified.
Requirement and applicability: Required
Application exceptions: Do not reassess the original historical B2 determination with a new score; distinguish verified reporting defects from unverified information.
Why this condition is needed: Even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown.
Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed. Reason for applying this to the PMS total-score comparison: even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown. No formal RoB2/GRADE/clinical certification was performed.

N15 · Were the primary-endpoint hierarchy, timing, and analysis plan specified in advance?

Required materials and conditions: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint
Conditions for verification: The dates, total score, timing, and hierarchy in the registration, protocol, and analysis plan are compared with the actual report.
Requirement and applicability: Required
Application exceptions: Do not treat failure to obtain the registration as confirmation of nonregistration or selective reporting.
Why this condition is needed: The presence of a total score in the paper does not verify its registered hierarchy.
Referenced methods: E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: the presence of a total score in the paper does not verify its registered hierarchy. No formal RoB2/GRADE/clinical certification was performed.

N16 · Can the flow of recruited, allocated, and analysed participants in the main trial be verified consistently?

Required materials and conditions: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group
Conditions for verification: Recruitment, allocation, completion, and analysis flow, and reasons for exclusion, are linked consistently across the abstract, methods, and tables.
Requirement and applicability: Required
Application exceptions: Do not invent specific overall participant counts from the abstract, Methods, or tables that are absent from the currently archived summary.
Why this condition is needed: Using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E01: M08 §8.1–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to. No formal RoB2/GRADE/clinical certification was performed.

N17 · Do the baseline and end-of-treatment means, SDs, and denominators in the main trial table belong to the specified total score?

Required materials and conditions: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers
Conditions for verification: The four means, four SDs, analysis headers by group, and direction of the total score in the currently preserved original table are accurately linked.
Requirement and applicability: Required
Application exceptions: Do not change SD to SE or use the 78 participants per group as the overall allocation count.
Why this condition is needed: This is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages. No formal RoB2/GRADE/clinical certification was performed.

N18 · Are the preserved arithmetic change contrast and end-of-treatment difference distinguished from the formal adjusted effect?

Required materials and conditions: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis
Conditions for verification: The original attribution of the -3.05-point change contrast and -2.98-point end-of-treatment difference is kept separate from the unverified formal estimator.
Requirement and applicability: Required
Application exceptions: Preserve the original historical values unchanged, without new calculations, imputation of correlations, or reconstruction of variances in this review.
Why this condition is needed: This is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast. No formal RoB2/GRADE/clinical certification was performed.

N19 · Are the formal between-group change contrast, adjustment method, and confidence interval verified?

Required materials and conditions: Original change-contrast analysis results, model, analysis population, variance, and CI
Conditions for verification: Verify the analysis population, adjustment, variance, CI, and actual timing of the between-group change contrast.
Requirement and applicability: Required
Application exceptions: Do not impute unverified correlations or variances, or treat an end-of-treatment interval as a change-contrast CI.
Why this condition is needed: A point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores.
Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: a point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores. No formal RoB2/GRADE/clinical certification was performed.

N20 · Is the B6-placebo between-group test of change verified separately from within-group tests and the overall three-group test?

Required materials and conditions: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan
Conditions for verification: The test of the change contrast, contrasts, and handling of multiplicity for the two selected groups are verified at their actual source locations.
Requirement and applicability: Required
Application exceptions: Do not reconstruct original P values or post hoc test values absent from the preserved archived summary, or treat nonsignificance as an effect of 0.
Why this condition is needed: Within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups.
Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups. No formal RoB2/GRADE/clinical certification was performed.

N21 · Are the analysis population, missing data, attrition, and definition of the effect of interest verified?

Required materials and conditions: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications
Conditions for verification: Allocation, completion, and analysis by group are linked to missing-data handling and the effect of interest.
Requirement and applicability: Required
Application exceptions: Do not label an unknown analysis as ITT or PP, or treat missing data as 0.
Why this condition is needed: This is needed to avoid treating an analysis of completers as an effect of assignment or as ITT.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating an analysis of completers as an effect of assignment or as ITT. No formal RoB2/GRADE/clinical certification was performed.

N22 · Are the supportive trial's allocation, completion, and endpoint denominators and its 30-symptom results distinguished?

Required materials and conditions: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results
Conditions for verification: Verify separately the original attribution of S02 allocation, completion, and endpoint analysis denominators and the 30-symptom score.
Requirement and applicability: Required
Application exceptions: Do not establish completion counts as endpoint denominators or combine arithmetic contrasts from different scales.
Why this condition is needed: Treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results. No formal RoB2/GRADE/clinical certification was performed.

N23 · Is there evidence supporting conversion of the 12-symptom and 30-symptom scales for comparison in the same effect units?

Required materials and conditions: The two original scales, score ranges, validation, and evidence for the validity of conversion
Conditions for verification: Verify the composition, ranges, and validation of the two scales, and justified conversion to a common unit of interpretation.
Requirement and applicability: Required
Application exceptions: Do not newly calculate a common scale, pooled result, or standardized effect.
Why this condition is needed: Comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales. No formal RoB2/GRADE/clinical certification was performed.

N24 · Have the original Results location, scale, denominators, and dispersion for the carried-forward 80 mg/day values been recovered?

Required materials and conditions: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record
Conditions for verification: The exact original Results location, scale, denominators by stage and arm, and dispersion are linked to the carried-forward values.
Requirement and applicability: Required
Application exceptions: Do not relabel 160 as the randomized count or 94 as a per-arm count, or invent an SD, CI, or P for -0.87 points.
Why this condition is needed: This is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication.
Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed.

N25 · Is the 2020 correction distinguished as an authorship change, an efficacy-number correction, or a retraction?

Required materials and conditions: The changes and author list in the correction document, and its link to the original article
Conditions for verification: The actual type of correction event and its link to the original trial are stated explicitly.
Requirement and applicability: Required
Application exceptions: Do not reassess the study effect or independence score solely because of an authorship change.
Why this condition is needed: This is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction. No formal RoB2/GRADE assessment or clinical certification was performed.

N26 · Do the 1999 review's 9 trials and 940 participants all represent the same eligible comparison?

Required materials and conditions: S01's included-trial table, interventions, populations, endpoints, and links to original reports
Conditions for verification: Verify each included trial's ingredients, population, comparator, endpoints, and whether it shares a cohort with another trial report.
Requirement and applicability: Required
Application exceptions: Do not automatically remove multivitamin or mastalgia-only trials and then calculate a new eligible count.
Why this condition is needed: This is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison.
Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / C04: M03 §3.2.1; detailed population conditions are custom designs / C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison. No formal RoB2/GRADE assessment or clinical certification was performed.

N27 · Can the definition, denominator, and comparator represented by the review's improvement OR 2.15 be verified?

Required materials and conditions: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table
Conditions for verification: Link the improvement definition, monotherapy subgroup, denominators, effect direction, and CI to the original material.
Requirement and applicability: Required
Application exceptions: Do not convert the OR to an RR, score change, or probability, or recalculate it.
Why this condition is needed: This is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success. No formal RoB2/GRADE assessment or clinical certification was performed.

N28 · Are reports from the same trial, protocols, and possible cohort overlaps identified?

Required materials and conditions: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials
Conditions for verification: Link the established relationships of S03/S11 and S08/S21 and the unverified relationship of S19/S02 to their respective original locations.
Requirement and applicability: Required
Application exceptions: Do not turn unverified overlap into confirmed independence or a confirmed shared cohort.
Why this condition is needed: This is needed to avoid double-counting reports or protocols as independent trials.
Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid double-counting reports or protocols as independent trials. No formal RoB2/GRADE assessment or clinical certification was performed.

N29 · Are the boundaries between overall results that are not favorable, emotional-domain results, and other interventions identified?

Required materials and conditions: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators
Conditions for verification: The limited findings of Doll and Kendall and the roles of active comparators, combinations, and other interventions are distinguished from overall results.
Requirement and applicability: Required
Application exceptions: Do not convert nonsignificance or unverified overall results into an effect of 0 or equivalence.
Why this condition is needed: This is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application / E09: M03 §3.2.4; custom limits on extrapolation. Reason for applying this to the overall PMS score comparison: this is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success. No formal RoB2/GRADE assessment or clinical certification was performed.

N30 · Are research funding, product supply, and conflict-of-interest declarations verified separately from independent funding?

Required materials and conditions: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations
Conditions for verification: For each trial, link the respective verified scope and unresolved details of funding, supply, and COI.
Requirement and applicability: Required; interpretation of independence
Application exceptions: Do not turn unverified interests into confirmed independence or automatic exclusion.
Why this condition is needed: A declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication.
Referenced methods: C10: Chamgap's own independence and attribution conditions. The formal methods sections used in this pilot do not warrant all of these detailed items. Reason for applying this to the overall PMS score comparison: a declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed.

N31 · Are adverse-event collection, denominators, and follow-up verified for the same PMS population and exposure?

Required materials and conditions: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials
Conditions for verification: Trial-specific AE definitions, systematic collection, exposure denominators, duration, and discontinuations are verified.
Requirement and applicability: Supplementary; required for interpreting safety
Application exceptions: Do not delete efficacy materials or fill unreported harm counts or risks with 0.
Why this condition is needed: This is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety.
Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H01: M19 §19.1.2–19.2.4; detailed distinctions are custom designs / H04: M19 §19.1.2–19.2.4; custom application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety. No formal RoB2/GRADE assessment or clinical certification was performed.

N32 · Are general B6 neuropathy warnings distinguished from risk estimates in PMS trials?

Required materials and conditions: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up
Conditions for verification: Separate the population, cumulative exposure, and scope of general warnings from the unverified direct PMS harm evidence.
Requirement and applicability: Supplementary; required for extrapolating harms
Application exceptions: Do not turn reports below 50 mg/day into a threshold below which no harm occurs or a risk estimate covering all low doses.
Why this condition is needed: It has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations.
Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H04: M19 §19.1.2–19.2.4; custom application / H08: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: it has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations. No formal RoB2/GRADE assessment or clinical certification was performed.

N33 · Are the EFSA upper limit and Australia's future regulation distinguished from treatment doses and current regulations?

Required materials and conditions: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date
Conditions for verification: The nature of 12 mg/day as an upper limit for total intake and the time boundary of the scheduled effective date, 2027-06-01, are kept distinct.
Requirement and applicability: Supplementary; indication of regulatory and safety scope
Application exceptions: Present this as the record at the original cutoff, without performing a current-law lookup or creating a dose recommendation in this review.
Why this condition is needed: The upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E10: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: the upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs. No formal RoB2/GRADE assessment or clinical certification was performed.

N34 · Are statistical magnitude, clinical importance, and other clinical questions kept separate?

Required materials and conditions: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question
Conditions for verification: Verified clinical importance and applicability for the overall PMS endpoint are distinguished from unresolved details.
Requirement and applicability: Required
Application exceptions: Do not recalculate the historical g=-0.53 and -0.52559 or C·50, or use them as condition-status scores.
Why this condition is needed: This is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy.
Referenced methods: E05: M15 §15.3.1–15.3.3; custom application / E09: M03 §3.2.4; custom limits on extrapolation / E08: M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom designs. Reason for applying this to the overall PMS score comparison: this is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy. No formal RoB2/GRADE assessment or clinical certification was performed.

N35 · Is actual reading of local summaries distinguished from past access, external materials not read in this review, and the associated dates?

Required materials and conditions: Records of actual access, acquisition, and reading events, with material-specific dates and original locations
Conditions for verification: Reading of currently archived summaries, report-specific historical access declarations, blank access dates, the original review date, and external access not attempted in this review are distinguished.
Requirement and applicability: Required
Application exceptions: Do not treat a historical failed direct connection as an access failure in this review, or fill in missing date keys arbitrarily.
Why this condition is needed: This is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review.
Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design. Reason for applying this to the overall PMS score comparison: this is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review. No formal RoB2/GRADE assessment or clinical certification was performed.

N36 · Are the original C·50 assessment and the different verdict and policy of historical composite record 127 kept separate from current condition statuses?

Required materials and conditions: Current judgment, relationships to related records, original axes and version metadata
Conditions for verification: Preserve the original C·50, axes, related document quality and historical relationship to 127, without repurposing grades/axes/scores for new judgments.
Requirement and applicability: Required
Application exceptions: From 127, do not repurpose the B·60 judgment or pregnancy-nausea evidence, and do not open the original 127 file in this task.
Why this condition is needed: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table.
Referenced methods: C01: Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules. Reason for applying this to the overall PMS score comparison: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table. No official RoB2/GRADE assessment or clinical certification was performed.

N37 · Are statements of insufficiency or uncertainty linked to the scope of preservation, reference date and conditions for updating?

Required materials and conditions: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event
Conditions for verification: Record the original reference date, the date of the current review, the scope of what remains unverified and specific update events.
Requirement and applicability: Required
Application exceptions: Do not label search, selection or calculation files in the old ZIP as materials actually read in this task.
Why this condition is needed: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search.
Referenced methods: C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules / E06: M08 Table 8.2.a, M04 §4.6.3; self-designed application. Reason for applying this to the overall PMS score comparison: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search. No official RoB2/GRADE assessment or clinical certification was performed.

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 of the intervention.
Extent of review: Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification.

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 a result was not reported.
Extent of review: Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification.

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

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

Referenced principle: Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement and selective reporting.
Extent of review: Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification.

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: Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification.

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.
Extent of review: Historical reuse, from 1585, of the original-byte/SHA inspection copies and principles of the 5 methodological HTML documents. This is not a new reading of the full methods texts or an official assessment/certification.

What the statuses mean

Met: The specific narrow condition concerning identity, attribution of numbers, records or interpretive boundaries is met. This does not certify a clinical effect, absence of risk or current verification of external full texts.
Partly verified: Some substantive content is available, but verification of the question’s product, diagnosis, denominators, analysis/materials is incomplete.
Unverified: Cannot be established within the currently preserved scope. This does not mean an effect of 0, absence of research worldwide or an access failure in this task.
Conflicting records: Inconsistent reports of the same fact remain. Successful preservation of a conflict is distinguished from verification of actual consistency.
Not reported: Not reported only within the explicitly identified content obtained at that time. Do not extend this to the entire full text that has not been read in this task.
Not applicable: Use only when there is a reason the condition does not apply to the current claim. This is not a substitute for unverified or unread.
Inaccessible: Distinguish an actual failure in this task from a historical failure. Do not assign this to external materials not attempted in this task.
Review incomplete: Limited to the fact that current external comparison has not been performed. This does not mean that reading of the local archived summaries or individual judgments actually completed is incomplete.

Change history

2026-11-01 · Public page/material version 1.0

The public view and materials were prepared from the existing 37 items. No new clinical search, change in verification status or scoring was performed.

The stored-material review date (2026-10-05) and original evidence cut-off (2026-09-15) were retained unchanged.

Researcher downloads

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

View all item details

N01 · Which population, intervention, comparator, and endpoint define the distinct claim?

Current findings: The original claim is “reduction of overall symptom severity in diagnosed PMS.” Oral B6-only tablets are compared with placebo in nonpregnant adults; PMDD, pregnancy nausea, and individual symptoms are not the direct claim.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The scope and identity conditions are met. This does not mean that symptom improvement or the efficacy of a particular dose has been established.
Reason for missing information: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint
Required materials and conditions: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint
Materials to obtain first: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint
Further research: Compare the current manuscript with each trial's population, intervention, comparator, and endpoint, and record the reason for a change only if a boundary has changed.
Remaining uncertainty: Dated records linking the original claim to the actual eligibility criteria, comparison, and endpoint: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The current /ko/effect is linked to the boundaries of nonpregnant PMS, oral B6 monotherapy, placebo, and overall symptom score.
Why this condition is needed: The current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea.
Application exceptions: Evidence for PMDD, individual emotional symptoms, mastalgia, or pregnancy nausea is not transferred to the current claim.
Referenced methods: C01: question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C04: M03 §3.2.1; detailed population conditions are self-designed / C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are self-designed. Reason for applying these to this overall PMS score comparison: the current overall-symptom comparison must be separated from the historical claim that combined PMS and pregnancy nausea. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03

N02 · Are the prospectively confirmed PMS population, modern diagnostic assessment, and differentiation from PMDD verified?

Current findings: The main trial involved nonpregnant adults aged 18–45 and used prospective diaries over two diagnostic cycles. Deficiency status, detailed differentiation from PMDD, and modern diagnostic adjudication remain unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The diaries and age range are preserved, but the detailed diagnosis and baseline status have not all been verified.
Reason for missing information: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status
Required materials and conditions: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status
Materials to obtain first: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status
Further research: First compare the diagnostic procedures across trials, then examine comparative records for PMS populations confirmed using the same definition.
Remaining uncertainty: Inclusion and exclusion criteria, actual diagnostic diaries, and information on PMDD differentiation and baseline nutritional status: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The diagnostic cycles, participant ages and selection, differentiation from PMDD, and baseline nutritional status are linked to actual records.
Why this condition is needed: Self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population.
Application exceptions: Unverified diagnostic details are not taken to mean that no PMS population exists or that treatment is ineffective for PMDD.
Referenced methods: C04: M03 §3.2.1; detailed population conditions are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: self-reported premenstrual symptoms and diagnosed PMS or PMDD cannot be treated as the same population. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03

N03 · Is the main trial's B6-only arm distinguished from the Hypericum and placebo arms?

Current findings: S03 has separate parallel arms for B6 alone, Hypericum, and placebo. The current comparison uses only B6 and placebo and does not add the effect of Hypericum.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The arm composition and attribution of the selected comparison are preserved. The conditions for verifying allocation concealment and dose have not thereby also been met.
Reason for missing information: Original records of each arm's intervention list, regimen, and comparator composition
Required materials and conditions: Original records of each arm's intervention list, regimen, and comparator composition
Materials to obtain first: Original records of each arm's intervention list, regimen, and comparator composition
Further research: Check the interventions table by arm and classify monotherapy, combination therapy, and comparisons with other ingredients separately.
Remaining uncertainty: Original records of each arm's intervention list, regimen, and comparator composition: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The actual parallel-arm composition is distinguished from the B6-versus-placebo comparison to be used in this table.
Why this condition is needed: Reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution.
Application exceptions: The use of Hypericum in another arm is not taken to imply concurrent administration in the B6-only arm.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E01: M08 §8.1–8.2.3; self-applied / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: reading the two ingredients in the paper's title as a combination regimen changes the attribution of the intervention's contribution. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S03

N04 · Are the vitamer and salt of B6 in the key trials verified?

Current findings: The exact vitamer and salt in the key trials remain unverified. The manuscript states that B6 is not the name of a single molecule and that pyridoxine, pyridoxal, and PLP were not treated as identical.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: General ingredient descriptions do not establish the identity of the actual trial product.
Reason for missing information: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials
Required materials and conditions: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials
Materials to obtain first: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials
Further research: Cross-check the original trial's product identity records, and examine records for other vitamers as distinct exposures.
Remaining uncertainty: Product ingredient lists, manufacturing specifications, and vitamer and salt records for the key trials: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the vitamer and salt of the product actually administered using trial-specific documents or manufacturing records.
Why this condition is needed: Pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures.
Application exceptions: The trial's salt is not filled in from common commercial products or general NIH descriptions.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: pyridoxine, pyridoxal, PLP, and salts cannot be recast as chemically identical exposures. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03 S15

N05 · Are details of the actual tablets, such as brand, origin, batch, and release form, verified?

Current findings: The route is oral and the formulation is a tablet. Manufacturing origin, brand, crystal form, release form, and batch remain unverified or inconsistently described.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Only the route and broad formulation have been verified; detailed product equivalence has not been established.
Reason for missing information: Manufacturing, product, batch, and release-form specifications for the administered tablets
Required materials and conditions: Manufacturing, product, batch, and release-form specifications for the administered tablets
Materials to obtain first: Manufacturing, product, batch, and release-form specifications for the administered tablets
Further research: Obtain trial-product documents to examine differences between formulations; do not substitute another commercial product.
Remaining uncertainty: Manufacturing, product, batch, and release-form specifications for the administered tablets: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the oral route and actual product, batch, and release form, and distinguish the unverified dimensions.
Why this condition is needed: The fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions.
Application exceptions: Unverified origin or brand is not converted into a finding that another product lacks efficacy.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed. Reason for applying this to this overall PMS score comparison: the fact that a product is an oral tablet alone does not establish equivalence in release, strength, or manufacturing conditions. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03

N06 · Are the main trial's tablet strength and total daily dose consistently verified?

Current findings: The main trial's tablet-strength descriptions conflict, leaving the total daily dose unverified. The currently retained archived summary preserves the fact of the conflict, but does not contain the specific conflicting tablet-strength numbers or original statements.
Verification status: Conflicting records
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Consistency of the actual daily dose remains unresolved. Successfully recording the conflict is distinguished from verifying the exposure.
Reason for missing information: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose
Required materials and conditions: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose
Materials to obtain first: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose
Further research: Compare the original dosing documents and revision history to verify a consistent exposure record, without calculating a new dose.
Remaining uncertainty: Author confirmation of the conflicting original strength statements, dosing table, number of tablets per administration, frequency, and total daily dose: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Tablet strength, number of tablets, frequency, total daily dose, and the basis for conversion are linked consistently.
Why this condition is needed: Conflicting descriptions of the study dose limit interpretation of the actual exposure and dose.
Application exceptions: Do not reconstruct numbers absent from the conflicting original statements or use the study dose as dosing instructions.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: conflicting descriptions of the study dose limit interpretation of the actual exposure and dose. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S03

N07 · Is the supportive trial's daily B6 dose verified separately from the magnesium dose of 250 mg?

Current findings: The retained S02 content explicitly states that the B6 dose could not be verified in the report. 250 mg refers to magnesium, not the daily dose in the B6-only arm.
Verification status: Not reported
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The dose is described as not reported only within the supportive trial report content obtained at the time. This is not the result of a new check of the entire full text.
Reason for missing information: S02 records of the B6 dosing regimen and product, and the original dose statement
Required materials and conditions: S02 records of the B6 dosing regimen and product, and the original dose statement
Materials to obtain first: S02 records of the B6 dosing regimen and product, and the original dose statement
Further research: Compare the regimens by arm in S02 and extract the magnesium and B6 values separately.
Remaining uncertainty: S02 records of the B6 dosing regimen and product, and the original dose statement: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: In S02, verify the actual B6 amount at its original location, and keep it separate from the magnesium dose.
Why this condition is needed: Transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure.
Application exceptions: 250 mg is not relabeled as a B6 value. The absence of reporting is not generalized to the entire full text, which was not read in this review.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: transferring the magnesium amount from another arm to the B6 dose misattributes the product and exposure. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02

N08 · Are the diagnostic and treatment cycles and information on actual administration and adherence verified?

Current findings: The main trial is preserved as 2 diagnostic recording cycles followed by 2 treatment cycles, with administration throughout the cycle. Actual adherence and arm-specific discontinuation and dosing changes remain unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: A nominal cycle schedule is available, but actual exposure received and adherence have not all been verified.
Reason for missing information: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment
Required materials and conditions: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment
Materials to obtain first: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment
Further research: Compare the cycle schedule with actual administration records and examine deviations in relation to the actual effect of interest.
Remaining uncertainty: Cycle-specific records of administration, adherence, discontinuation, and rescue treatment: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the two diagnostic cycles, two treatment cycles, administration throughout the cycle, and actual adherence and discontinuation as distinct matters.
Why this condition is needed: Diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence.
Application exceptions: The two cycles are not converted into a fixed number of days or an optimal treatment duration.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied / E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying these to this overall PMS score comparison: diagnostic records across menstrual cycles must be separated from treatment exposure and the period of adherence. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S03

N09 · Is there direct evidence of sustained effects and long-term outcomes after treatment ends?

Current findings: The current manuscript leaves sustained long-term effects unverified. It does not claim that effects persisting after discontinuation have been verified from the two-treatment-cycle comparison alone.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The currently archived material contains no direct estimate of sustained effects or follow-up information.
Reason for missing information: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale
Required materials and conditions: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale
Materials to obtain first: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale
Further research: Define sustained effects as a separate question and examine comparative follow-up records after discontinuation.
Remaining uncertainty: Follow-up schedules after treatment discontinuation and comparative outcomes on the same overall-symptom scale: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Follow-up time points, post-discontinuation outcomes, and sustained effects are linked through separate direct evidence.
Why this condition is needed: Needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects.
Application exceptions: A long-term trial is not made mandatory for every study addressing the current narrow question of two cycles.
Referenced methods: E08: M03 §3.2.1–3.2.4; details on dose, duration, and effect modification are self-designed. Reason for applying this to this overall PMS score comparison: this is needed to avoid extending a symptom comparison over two treatment cycles to a claim of sustained long-term effects. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03

N10 · Is the actual comparison in terms of placebo, common drug regimens, and concomitant treatments verified?

Current findings: The main trial's placebo is preserved as lactose and cellulose. The fixed common drug regimen and arm-specific concomitant and rescue treatments remain unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Placebo composition has been verified, but the influence of other treatments and equivalence of background treatment have not all been verified.
Reason for missing information: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes
Required materials and conditions: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes
Materials to obtain first: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes
Further research: Cross-check the actual comparator composition and background treatment to examine attribution of intervention differences.
Remaining uncertainty: Placebo manufacturing records and arm-specific records of medicines, supplements, rescue treatment, and changes: limited to the currently retained record, with no new assessment of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Distinguish placebo composition and common treatment from arm-specific concomitant treatments and changes using actual records.
Why this condition is needed: Needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy.
Application exceptions: Do not assume that all changes in both arms are identical or fill an unverified field with an assertion of no concomitant treatment.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are self-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; self-applied. Reason for applying these to this overall PMS score comparison: this is needed to avoid attributing differences in background treatment to an additional effect of B6 monotherapy. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S03

N11 · Are the allocation process, allocation concealment, and baseline balance verified?

Current findings: The main trial is preserved as a parallel-group design, and baseline total scores are also available. Unverified allocation concealment or registration was not asserted to be actual absence; detailed allocation and analysis flow remain unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Some design and score information is available, but the sequence, concealment, and overall baseline balance could not all be verified.
Reason for missing information: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records
Required materials and conditions: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records
Materials to obtain first: Allocation sequence, concealment procedures, arm-specific baseline characteristics, and participant-flow records
Further research: Compare the original methods and allocation records with baseline characteristics relevant to the outcome, and record what was actually verified.
Remaining uncertainty: Allocation sequence, concealment procedures, baseline characteristics by group, and flow data; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The random sequence, concealment, selection stages, and baseline balance relevant to the outcome are linked to their actual source locations.
Why this condition is needed: An RCT label alone does not establish that errors in the allocation process or confounding have been resolved.
Application exceptions: Do not assert that unverified allocation concealment was actually absent.
Referenced methods: E01: M08 §8.1–8.2.3; custom application. Reason for applying this to the PMS total-score comparison: an RCT label alone does not establish that allocation errors or confounding have been resolved. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N12 · Are blinding and collection procedures by group verified for the subjective diary assessment?

Current findings: The currently archived material identifies a 12-symptom diary endpoint but does not contain specific details of how blinding was implemented or how diaries were collected by group.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Details of the measurement procedures cannot be verified within the summaries and structure currently saved.
Reason for missing information: Diary collection manual, blinding, assessment, and measurement schedules by group
Required materials and conditions: Diary collection manual, blinding, assessment, and measurement schedules by group
Materials to obtain first: Diary collection manual, blinding, assessment, and measurement schedules by group
Further research: Compare the methods section with the diary procedures and review the actual collection limitations for the subjective endpoint.
Remaining uncertainty: Diary collection manual, blinding, assessment, and measurement schedules by group; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the actual procedures for diary completion, collection timing, assessors, and blinding by group.
Why this condition is needed: For patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score.
Application exceptions: Do not use unverified blinding information to establish blinding failure or the magnitude of bias.
Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: for patient-reported endpoints, differences in expectations or collection procedures may be reflected in the total score. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N13 · Are the definition, direction, and aggregation range of the total 12-symptom diary score verified?

Current findings: The main trial uses the total score of a 12-symptom diary, with lower scores indicating better outcomes. Total-score normalization and aggregation range remain unverified, and the manuscript does not call the older scale DRSP.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The composition and direction are preserved, but a reproducible definition of the total-score calculation remains incomplete.
Reason for missing information: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials
Required materials and conditions: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials
Materials to obtain first: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials
Further research: Compare the original score definitions and distinguish the total score from subdomains and other scales.
Remaining uncertainty: Original diary, scoring sheet, aggregation and normalization specifications, and scale validation materials; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the direction, composition, aggregation range, and scale name of the 12-symptom total score against the actual material.
Why this condition is needed: This is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score.
Application exceptions: Do not call the older diary DRSP or transfer significance in a subdomain to the overall endpoint.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the study-specific total score as the modern DRSP or an individual emotional-symptom score. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N14 · Can the total-score calculation and normalization be verified reproducibly?

Current findings: The original B2 rationale identifies a reporting and measurement problem: the explanation of total-score calculation and normalization is insufficiently reproducible. The currently archived summary does not contain the calculation formula.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The process used to generate the score cannot be reproduced within the currently preserved material.
Reason for missing information: Raw symptom scores, calculation formula, and rules for missing data and normalization
Required materials and conditions: Raw symptom scores, calculation formula, and rules for missing data and normalization
Materials to obtain first: Raw symptom scores, calculation formula, and rules for missing data and normalization
Further research: Compare the score-calculation documentation with the original table to review interpretability, without calculating a new score.
Remaining uncertainty: Raw symptom scores, calculation formula, and rules for missing data and normalization; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The calculation, missing-data handling, and normalization methods from individual symptom records through to the total score are verified.
Why this condition is needed: Even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown.
Application exceptions: Do not reassess the original historical B2 determination with a new score; distinguish verified reporting defects from unverified information.
Referenced methods: E03: M08 Table 8.2.a, M03 §3.2.4; custom application / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed. Reason for applying this to the PMS total-score comparison: even when means are available, interpretation of the measurement remains limited if the process used to generate the total score is unknown. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N15 · Were the primary-endpoint hierarchy, timing, and analysis plan specified in advance?

Current findings: The registered hierarchy of the main trial's total score remains unverified. S02 has the identifier IRCT201106216854N1, but registration details, history, and whether registration was prospective could not be verified.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The existence of an identifier alone cannot verify agreement between the prospective plan and the actual report.
Reason for missing information: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint
Required materials and conditions: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint
Materials to obtain first: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint
Further research: Compare plan versions and dates with the actual overall endpoint and analysis, and record what remains unchecked.
Remaining uncertainty: Dated registration, protocol, and analysis plan, and the results table for the overall endpoint; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The dates, total score, timing, and hierarchy in the registration, protocol, and analysis plan are compared with the actual report.
Why this condition is needed: The presence of a total score in the paper does not verify its registered hierarchy.
Application exceptions: Do not treat failure to obtain the registration as confirmation of nonregistration or selective reporting.
Referenced methods: E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: the presence of a total score in the paper does not verify its registered hierarchy. No formal RoB2/GRADE/clinical certification was performed.

Related sources S02 S03 S18

N16 · Can the flow of recruited, allocated, and analysed participants in the main trial be verified consistently?

Current findings: The table analysis headers show B6 78 participants and placebo 78 participants. The manuscript states that internally inconsistent participant accounting across the abstract, methods, and tables makes a coherent analysis-population check difficult. Detailed recruitment and allocation counts are absent from the current summary.
Verification status: Conflicting records
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The actual inconsistency in denominator flow remains unresolved, and the table denominators are not transferred to other stages.
Reason for missing information: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group
Required materials and conditions: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group
Materials to obtain first: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group
Further research: Link each stage-specific and endpoint-specific denominator to its original location to check consistency only, without creating new participant totals.
Remaining uncertainty: Conflicting recruitment, allocation, completion, and analysis flow diagrams, and reasons for exclusion by group; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Recruitment, allocation, completion, and analysis flow, and reasons for exclusion, are linked consistently across the abstract, methods, and tables.
Why this condition is needed: Using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to.
Application exceptions: Do not invent specific overall participant counts from the abstract, Methods, or tables that are absent from the currently archived summary.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E01: M08 §8.1–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: using the table's 78 participants per group as overall recruitment or allocation counts changes which stage the denominator belongs to. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N17 · Do the baseline and end-of-treatment means, SDs, and denominators in the main trial table belong to the specified total score?

Current findings: The preserved table shows B6 33.93(SD 6.95)→20.92(SD 5.26), placebo 33.86(SD 6.16)→23.90(SD 6.00), with analysis headers of 78 participants per group. All are study-specific total scores.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The types, endpoints, and table-denominator attribution of the currently preserved numbers have been verified. This does not mean that the original full text was newly checked or that allocation flow was resolved.
Reason for missing information: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers
Required materials and conditions: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers
Materials to obtain first: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers
Further research: Check the original locations of numbers, dispersion, and denominators, and preserve both the prior and revised values if corrections are made.
Remaining uncertainty: Original total-score table, definitions of dispersion for each value, and endpoint-specific analysis headers; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The four means, four SDs, analysis headers by group, and direction of the total score in the currently preserved original table are accurately linked.
Why this condition is needed: This is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages.
Application exceptions: Do not change SD to SE or use the 78 participants per group as the overall allocation count.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to preserve the original table's means, dispersion, and analysis headers without transferring them to other endpoints or stages. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N18 · Are the preserved arithmetic change contrast and end-of-treatment difference distinguished from the formal adjusted effect?

Current findings: In the manuscript, -3.05 points is the historical arithmetic change contrast derived from reported means, and -2.98 points is the end-of-treatment difference. These are not a formal adjusted change contrast or its confidence interval, and they were not recalculated in this review.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The type of historical arithmetic and its boundary with the formal estimator have been verified. This does not mean that the conditions for causal effect or precision have been met.
Reason for missing information: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis
Required materials and conditions: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis
Materials to obtain first: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis
Further research: Perform only a traceability review comparing historical calculations with formal results, without producing new arithmetic values or CIs.
Remaining uncertainty: Original calculation records C03·C04, the original table, and specifications for the formal change-contrast analysis; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The original attribution of the -3.05-point change contrast and -2.98-point end-of-treatment difference is kept separate from the unverified formal estimator.
Why this condition is needed: This is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast.
Application exceptions: Preserve the original historical values unchanged, without new calculations, imputation of correlations, or reconstruction of variances in this review.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating the arithmetic contrast from reported means as the same estimator as a formal adjusted change contrast. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N19 · Are the formal between-group change contrast, adjustment method, and confidence interval verified?

Current findings: Formal change-contrast confidence intervals remain unverified for the main and supportive trials. The manuscript retains the limitations that ANCOVA was not reported and correlations or variances were not estimated.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The formal change-contrast analysis and its interval cannot be verified within the currently preserved material.
Reason for missing information: Original change-contrast analysis results, model, analysis population, variance, and CI
Required materials and conditions: Original change-contrast analysis results, model, analysis population, variance, and CI
Materials to obtain first: Original change-contrast analysis results, model, analysis population, variance, and CI
Further research: Compare the original results and analysis plan to verify the reported interval for the same estimator, without calculating a new interval.
Remaining uncertainty: Original change-contrast analysis results, model, analysis population, variance, and CI; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify the analysis population, adjustment, variance, CI, and actual timing of the between-group change contrast.
Why this condition is needed: A point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores.
Application exceptions: Do not impute unverified correlations or variances, or treat an end-of-treatment interval as a change-contrast CI.
Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the PMS total-score comparison: a point estimate or end-of-treatment SD alone cannot establish the precision of the effect on change scores. No formal RoB2/GRADE/clinical certification was performed.

Related sources S02 S03

N20 · Is the B6-placebo between-group test of change verified separately from within-group tests and the overall three-group test?

Current findings: The manuscript states that within-group significance or the overall three-group test result was not substituted for the exact B6-placebo test of the change contrast. The currently archived summary does not contain the specific P value of that original test.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The limitations on test attribution have been preserved, but the exact test of change between the two groups and the handling of multiplicity remain unverified.
Reason for missing information: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan
Required materials and conditions: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan
Materials to obtain first: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan
Further research: Identify the comparisons in the original test table and review within-group tests, the overall test, and the test of the two selected groups separately.
Remaining uncertainty: Original tests, post hoc contrasts, handling of multiplicity, and analysis plan; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: The test of the change contrast, contrasts, and handling of multiplicity for the two selected groups are verified at their actual source locations.
Why this condition is needed: Within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups.
Application exceptions: Do not reconstruct original P values or post hoc test values absent from the preserved archived summary, or treat nonsignificance as an effect of 0.
Referenced methods: E04: M08 §8.2.2, M15 §15.3.1; custom application / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the PMS total-score comparison: within-group significance and the overall three-group test are not a test of the change contrast between the two selected groups. No formal RoB2/GRADE/clinical certification was performed.

Related sources S03

N21 · Are the analysis population, missing data, attrition, and definition of the effect of interest verified?

Current findings: Detailed allocation and analysis flow remain unverified, and the main trial's table headers conflict with the overall participant-count description. In the supportive trial, completion counts and endpoint-specific analysis denominators may differ, so they are kept separate.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Direct specifications of the effect of interest and missing-data handling could not be verified in the current summary.
Reason for missing information: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications
Required materials and conditions: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications
Materials to obtain first: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications
Further research: Compare the analysis plan and flow diagram with the result denominators to distinguish the effect being estimated.
Remaining uncertainty: Endpoint-specific analysis populations, missing data, reasons for attrition, and ITT/PP and adjustment specifications; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Allocation, completion, and analysis by group are linked to missing-data handling and the effect of interest.
Why this condition is needed: This is needed to avoid treating an analysis of completers as an effect of assignment or as ITT.
Application exceptions: Do not label an unknown analysis as ITT or PP, or treat missing data as 0.
Referenced methods: C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E02: M03 §3.2.3, M08 §8.2.2–8.2.3; custom application / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: this is needed to avoid treating an analysis of completers as an effect of assignment or as ITT. No formal RoB2/GRADE/clinical certification was performed.

Related sources S02 S03

N22 · Are the supportive trial's allocation, completion, and endpoint denominators and its 30-symptom results distinguished?

Current findings: S02 allocated 42 participants per group; completers were B6 36 and placebo 37. The 30-symptom diary values B6 36.51→22.84 and placebo 35.80→28.41, and the historical arithmetic contrast of -6.28 points, are preserved, but endpoint-specific analysis denominators and the between-group change CI remain unverified.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Allocation and completion counts and scores are available, but endpoint denominators, variance, and formal intervals could not be established.
Reason for missing information: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results
Required materials and conditions: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results
Materials to obtain first: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results
Further research: Compare the original tables with allocation, completion, and analysis kept as separate stages, without recalculating the currently preserved historical arithmetic.
Remaining uncertainty: S02 endpoint-specific analysis headers, score tables, variance, missing data, and change-contrast results; scope is limited to the currently preserved record, with no new determination of clinical efficacy, individual probability of success, or safety.
Conditions for verification: Verify separately the original attribution of S02 allocation, completion, and endpoint analysis denominators and the 30-symptom score.
Why this condition is needed: Treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results.
Application exceptions: Do not establish completion counts as endpoint denominators or combine arithmetic contrasts from different scales.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is custom-designed / E04: M08 §8.2.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: treating 42 allocated participants, 36/37 completers, and endpoint analysis counts as the same denominator changes the attribution of results. No formal RoB2/GRADE/clinical certification was performed.

Related sources S02

N23 · Is there evidence supporting conversion of the 12-symptom and 30-symptom scales for comparison in the same effect units?

Current findings: The main trial uses a 12-symptom diary, and the supportive trial uses a separate 30-symptom diary. The manuscript does not combine -3.05 points and -6.28 points and provides no evidence supporting conversion to a common scale.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The fact that the scales differ has been verified, but comparability in the same clinical units remains unverified.
Reason for missing information: The two original scales, score ranges, validation, and evidence for the validity of conversion
Required materials and conditions: The two original scales, score ranges, validation, and evidence for the validity of conversion
Materials to obtain first: The two original scales, score ranges, validation, and evidence for the validity of conversion
Further research: Compare results separately by scale, and do not combine them into a common effect without validated evidence supporting conversion.
Remaining uncertainty: Materials on the two original scales, score ranges, validation, and validity of conversion. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Verify the composition, ranges, and validation of the two scales, and justified conversion to a common unit of interpretation.
Why this condition is needed: Comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales.
Application exceptions: Do not newly calculate a common scale, pooled result, or standardized effect.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptation is custom-designed / E03: M08 Table 8.2.a, M03 §3.2.4; custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the PMS total-score comparison: comparing numerical differences in different total scores as the same amount of improvement erases the differences between scales. No formal RoB2/GRADE/clinical certification was performed.

Related sources S02 S03

N24 · Have the original Results location, scale, denominators, and dispersion for the carried-forward 80 mg/day values been recovered?

Current findings: S06 preserves 80 mg/day, B6 -1.80 and placebo -0.93, an initial sample of 160 with 94 analysed, and the historical arithmetic change contrast of -0.87 points. The exact original Results location, scale, dispersion, and denominators by stage and arm remain unrecovered; these values were not used for grading or independent replication.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The carried-forward values and their limitations were preserved, but direct traceability to the original results and the analysis details could not be verified.
Reason for missing information: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record
Required materials and conditions: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record
Materials to obtain first: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record
Further research: First review the provenance of the existing numbers, and do not integrate them quantitatively before their identity and scope are recovered.
Remaining uncertainty: The original Results location, scale, denominators by arm and stage, and dispersion for S06, together with the original C10 calculation record. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: The exact original Results location, scale, denominators by stage and arm, and dispersion are linked to the carried-forward values.
Why this condition is needed: This is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication.
Application exceptions: Do not relabel 160 as the randomized count or 94 as a per-arm count, or invent an SD, CI, or P for -0.87 points.
Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid upgrading numbers retained in the resumption request to newly verified original results or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S06

N25 · Is the 2020 correction distinguished as an authorship change, an efficacy-number correction, or a retraction?

Current findings: S07 is a 2020 correction adding the omitted author Shahnaz Babayanzad Ahari. It was not described as an efficacy-number correction or a retraction, and it belongs to the same trial publication family as S06.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The correction type and trial relationship were distinguished in the retained record. The external full correction text has not been newly read in this review.
Reason for missing information: The changes and author list in the correction document, and its link to the original article
Required materials and conditions: The changes and author list in the correction document, and its link to the original article
Materials to obtain first: The changes and author list in the correction document, and its link to the original article
Further research: Compare only the items changed by correction or retraction documents; review changes to the original numbers only when separately verified.
Remaining uncertainty: The changes and author list in the correction document, and its link to the original article. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: The actual type of correction event and its link to the original trial are stated explicitly.
Why this condition is needed: This is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction.
Application exceptions: Do not reassess the study effect or independence score solely because of an authorship change.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E06: M08 Table 8.2.a, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid interpreting a correction adding an author as a correction to result numbers or a retraction. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S06 S07

N26 · Do the 1999 review's 9 trials and 940 participants all represent the same eligible comparison?

Current findings: The review's 9 trials and 940 participants include multivitamin trials and trials assessing mastalgia alone. They do not all represent the same comparison of overall PMS symptoms with B6 monotherapy, and they are not added up as independent studies in the current table.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The heterogeneous inclusion scope was identified, but detailed eligibility and cohort relationships could not be established for every trial.
Reason for missing information: S01's included-trial table, interventions, populations, endpoints, and links to original reports
Required materials and conditions: S01's included-trial table, interventions, populations, endpoints, and links to original reports
Materials to obtain first: S01's included-trial table, interventions, populations, endpoints, and links to original reports
Further research: Compare the included trials against each question, and do not use review totals as the number of study families or the denominator for the current effect.
Remaining uncertainty: S01's included-trial table, interventions, populations, endpoints, and links to original reports. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Verify each included trial's ingredients, population, comparator, endpoints, and whether it shares a cohort with another trial report.
Why this condition is needed: This is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison.
Application exceptions: Do not automatically remove multivitamin or mastalgia-only trials and then calculate a new eligible count.
Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / C04: M03 §3.2.1; detailed population conditions are custom designs / C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid counting the review totals as independent repetitions of the same B6-only PMS trial comparison. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S01

N27 · Can the definition, denominator, and comparator represented by the review's improvement OR 2.15 be verified?

Current findings: For the B6-only subgroup, an improvement OR of 2.15 (CI 1.79–2.59) is retained. It is not a percentage reduction in the overall symptom score or an individual's probability of improvement. The currently archived summary does not contain a table of improvement classifications or subgroup events and denominators.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The measure, subgroup, and interval are available, but traceability of the specific improvement definition and event denominators remains incomplete.
Reason for missing information: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table
Required materials and conditions: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table
Materials to obtain first: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table
Further research: Link the review's categorical results to the original table and review them separately from score results, without recalculating effects.
Remaining uncertainty: S01's definition of improvement, events in the monotherapy subgroup, comparator, denominators, and original OR table. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Link the improvement definition, monotherapy subgroup, denominators, effect direction, and CI to the original material.
Why this condition is needed: This is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success.
Application exceptions: Do not convert the OR to an RR, score change, or probability, or recalculate it.
Referenced methods: C06: M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom designs / C07: M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptations are custom designs / E04: M08 §8.2.2, M15 §15.3.1; custom application / E05: M15 §15.3.1–15.3.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading an odds ratio for improvement as a percentage reduction in the total score or an individual's probability of success. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S01

N28 · Are reports from the same trial, protocols, and possible cohort overlaps identified?

Current findings: S11 is grouped as an earlier partial report of S03, and S21 as the protocol for S08. Possible cohort overlap between S19 and S02 remains unverified, and it is not counted as independent replication of B6 monotherapy.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The two family links are present, but the actual cohort relationship of S19/S02 and the total unique participant count remain unverified.
Reason for missing information: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials
Required materials and conditions: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials
Materials to obtain first: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials
Further research: Link reports to trial families, distinguish confirmed, possible, and unknown relationships, and leave unverified unique participant counts blank.
Remaining uncertainty: A linkage table covering trial registration, sites, recruitment dates, participants, and reports, together with overlap materials. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Link the established relationships of S03/S11 and S08/S21 and the unverified relationship of S19/S02 to their respective original locations.
Why this condition is needed: This is needed to avoid double-counting reports or protocols as independent trials.
Application exceptions: Do not turn unverified overlap into confirmed independence or a confirmed shared cohort.
Referenced methods: C02: the distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a custom application / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid double-counting reports or protocols as independent trials. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03 S08 S11 S19 S21

N29 · Are the boundaries between overall results that are not favorable, emotional-domain results, and other interventions identified?

Current findings: Doll's emotional-domain signal is not transferred to overall improvement. Kendall's original overall mean and CI remain unverified. S08 involves an active comparator and inclusion of riboflavin; S09 concerns anxiety with a combination; S19 is a combination study; and S20 has no B6 arm. These are kept separate from the direct overall effect.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Contrary and scope-limited materials were retained, but the complete original overall results and detailed comparisons in older studies have not all been verified.
Reason for missing information: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators
Required materials and conditions: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators
Materials to obtain first: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators
Further research: Compare favorable, no-difference, and unfavorable results as materials addressing the same question, while separating results for other endpoints or interventions.
Remaining uncertainty: Overall and domain-specific outcome tables for each trial, with ingredients, comparators, and endpoint-specific denominators. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: The limited findings of Doll and Kendall and the roles of active comparators, combinations, and other interventions are distinguished from overall results.
Why this condition is needed: This is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success.
Application exceptions: Do not convert nonsignificance or unverified overall results into an effect of 0 or equivalence.
Referenced methods: C08: M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is a custom design / E07: M04 §4.6.1–4.6.2, M15 §15.3.1; custom application / E09: M03 §3.2.4; custom limits on extrapolation. Reason for applying this to the overall PMS score comparison: this is needed to avoid retaining only some favorable results or extrapolating emotional or anxiety domain results to overall PMS success. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S04 S05 S08 S09 S19 S20

N30 · Are research funding, product supply, and conflict-of-interest declarations verified separately from independent funding?

Current findings: S03 distinguishes the authors' declaration of no COI from the unverified specific funding and B6 supplier. In S02, supply of coded tablets by the university pharmacy was verified, but funding and author COI remain unverified. Other trials likewise retain their unresolved details within the available material scope.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Some supply and declaration details are available, but independent funding and all supply and employment relationships could not be established.
Reason for missing information: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations
Required materials and conditions: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations
Materials to obtain first: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations
Further research: Compare declarations separately with actual funding and supply materials, and record the limits on interpreting independence.
Remaining uncertainty: Trial-specific funding, product-supply agreements, author employment, patents, and COI declarations. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: For each trial, link the respective verified scope and unresolved details of funding, supply, and COI.
Why this condition is needed: A declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication.
Application exceptions: Do not turn unverified interests into confirmed independence or automatic exclusion.
Referenced methods: C10: Chamgap's own independence and attribution conditions. The formal methods sections used in this pilot do not warrant all of these detailed items. Reason for applying this to the overall PMS score comparison: a declaration of no conflicts of interest or pharmacy supply does not prove independent funding or independent replication. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03 S04 S05 S06

N31 · Are adverse-event collection, denominators, and follow-up verified for the same PMS population and exposure?

Current findings: The original safety explanation states that the absence of reports of serious adverse events in short trials does not establish long-term neurological safety. The currently retained archived summary does not contain complete AE collection tables, denominators, or discontinuation results for each PMS comparison.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: A complete harm comparison for the same population, actual dose, and duration could not be verified.
Reason for missing information: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials
Required materials and conditions: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials
Materials to obtain first: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials
Further research: Compare efficacy and harm outcomes separately, and review follow-up and collection methods suited to neurological outcomes.
Remaining uncertainty: Trial-specific AE definitions, collection, exposure denominators by arm, duration, and discontinuation materials. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Trial-specific AE definitions, systematic collection, exposure denominators, duration, and discontinuations are verified.
Why this condition is needed: This is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety.
Application exceptions: Do not delete efficacy materials or fill unreported harm counts or risks with 0.
Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H01: M19 §19.1.2–19.2.4; detailed distinctions are custom designs / H04: M19 §19.1.2–19.2.4; custom application / H06: M19 §19.1.2–19.2.4, M04 §4.6.3; custom application. Reason for applying this to the overall PMS score comparison: this is needed to avoid reading the absence of reported serious adverse events in a short trial as long-term safety. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03 S12 S13 S14 S16

N32 · Are general B6 neuropathy warnings distinguished from risk estimates in PMS trials?

Current findings: The retained TGA account records neuropathy reports even below 50 mg/day and warns about cumulative intake and potentially irreversible injury. This does not newly establish the incidence in PMS trials or comparative risk by specific vitamer or product.
Verification status: Partly verified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: General safety context is available, but there is no exposure, denominator, and risk comparison matching the PMS trials.
Reason for missing information: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up
Required materials and conditions: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up
Materials to obtain first: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up
Further research: Review general regulatory and safety-signal materials separately from direct comparative harm materials, and do not calculate new thresholds or risks.
Remaining uncertainty: Products, combined exposure, populations, duration, and denominators in neuropathy materials, together with PMS safety follow-up. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Separate the population, cumulative exposure, and scope of general warnings from the unverified direct PMS harm evidence.
Why this condition is needed: It has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations.
Application exceptions: Do not turn reports below 50 mg/day into a threshold below which no harm occurs or a risk estimate covering all low doses.
Referenced methods: E10: M19 §19.1.2–19.2.4; custom application / H04: M19 §19.1.2–19.2.4; custom application / H08: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: it has not been verified that official general safety information concerns the same exposure and population as the PMS trials, including their actual doses and durations. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S12 S13 S14 S16

N33 · Are the EFSA upper limit and Australia's future regulation distinguished from treatment doses and current regulations?

Current findings: The original cutoff is 2026-09-15. EFSA's adult 12 mg/day is an upper limit for chronic total intake; TGA's pharmacist-only change for above 50 mg~up to 200 mg/day is retained as scheduled to take effect on 2027-06-01. These are not treatment doses or current evidence of efficacy.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: Only the meaning and date boundaries of the retained regulatory and safety record were checked. This status does not newly certify current law or individual safety.
Reason for missing information: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date
Required materials and conditions: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date
Materials to obtain first: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date
Further research: Within an authorized update scope, compare document editions and effective dates, and keep them separate from treatment doses and biological thresholds.
Remaining uncertainty: The edition, publication/effective dates, and scope of the official documents, together with the original cutoff date. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: The nature of 12 mg/day as an upper limit for total intake and the time boundary of the scheduled effective date, 2027-06-01, are kept distinct.
Why this condition is needed: The upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs.
Application exceptions: Present this as the record at the original cutoff, without performing a current-law lookup or creating a dose recommendation in this review.
Referenced methods: C05: M03 §3.2.2–3.2.3; reverse-direction flagging and test adaptations are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design / E10: M19 §19.1.2–19.2.4; custom application / H09: Chamgap's own interpretation boundary. M19 principles are referenced; no formal causality tool is applied. Reason for applying this to the overall PMS score comparison: the upper limit for total nutrient intake and the effective date of sales rules are different facts from PMS treatment efficacy or a threshold below which no harm occurs. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S12 S14

N34 · Are statistical magnitude, clinical importance, and other clinical questions kept separate?

Current findings: The historical end-of-treatment Hedges g=-0.53 is a statistical-magnitude classification under the original scoring rubric, not a validated between-group MCID. Clinical importance and sustained benefit remain unverified, and this is not a verdict on PMDD or pregnancy nausea.
Verification status: Unverified
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The statistical value was preserved, but there is no validated clinical-importance criterion for this scale or direct evidence for events or other populations.
Reason for missing information: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question
Required materials and conditions: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question
Materials to obtain first: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question
Further research: Compare evidence on importance to patients and scale validation against the results, without inventing arbitrary thresholds or success probabilities.
Remaining uncertainty: Materials on a validated MCID, importance to patients, and applicability for the overall scale in question. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Verified clinical importance and applicability for the overall PMS endpoint are distinguished from unresolved details.
Why this condition is needed: This is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy.
Application exceptions: Do not recalculate the historical g=-0.53 and -0.52559 or C·50, or use them as condition-status scores.
Referenced methods: E05: M15 §15.3.1–15.3.3; custom application / E09: M03 §3.2.4; custom limits on extrapolation / E08: M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom designs. Reason for applying this to the overall PMS score comparison: this is needed to avoid turning the conventional magnitude of Hedges g into a validated MCID or a treatment benefit for PMDD or pregnancy. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S02 S03

N35 · Is actual reading of local summaries distinguished from past access, external materials not read in this review, and the associated dates?

Current findings: This review read the currently retained KO/EN manuscripts, 9 evidence entries, 21 bibliographic entries, and metadata. The original verified_date is 2026-09-15, and there is no actual-access-date key for each citation. Each material's access date is blank; the original review date is separate. External originals, separate indexes/ZIP files, and 127 were not read in this review.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: This condition records the boundary between actual local actions and historical declarations. It does not directly certify the current contents of external materials.
Reason for missing information: Records of actual access, acquisition, and reading events, with material-specific dates and original locations
Required materials and conditions: Records of actual access, acquisition, and reading events, with material-specific dates and original locations
Materials to obtain first: Records of actual access, acquisition, and reading events, with material-specific dates and original locations
Further research: Review access events separately for each material, and add current actions and dates only when new reading is authorized.
Remaining uncertainty: Records of actual access, acquisition, and reading events, with material-specific dates and original locations. Scope is limited to the currently retained records; no new judgment is made about clinical efficacy, an individual's probability of success, or safety.
Conditions for verification: Reading of currently archived summaries, report-specific historical access declarations, blank access dates, the original review date, and external access not attempted in this review are distinguished.
Why this condition is needed: This is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review.
Application exceptions: Do not treat a historical failed direct connection as an access failure in this review, or fill in missing date keys arbitrarily.
Referenced methods: C03: data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink contract are custom designs / C09: M04 §4.5, §4.6.3; limits on transitioning to current materials are based on the user's scope and custom design. Reason for applying this to the overall PMS score comparison: this is needed to avoid treating verified_date or historical access_level as an actual access date for each material in this review or as evidence of full-text reading in this review. No formal RoB2/GRADE assessment or clinical certification was performed.

Related sources S01 S02 S03 S04 S05 S06 S07 S08 S09 S10 S11 S12 S13 S14 S15 S16 S17 S18 S19 S20 S21

N36 · Are the original C·50 assessment and the different verdict and policy of historical composite record 127 kept separate from current condition statuses?

Current findings: The judgment in the current manuscript is C·50, with axes B/P/R1/I1/E+/B2/CX. The combined PMS/pregnancy-nausea record in 127 and its B·60 are related history and have not been repurposed for the current PMS-only claim. Preserve the numbers and original metadata of the current original judgment unchanged.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The separation of current/historical judgments and the rule that they remain unchanged were verified. C·50 is not used as evidence that individual conditions are met.
Reason for missing information: Current judgment, relationships to related records, original axes and version metadata
Required materials and conditions: Current judgment, relationships to related records, original axes and version metadata
Materials to obtain first: Current judgment, relationships to related records, original axes and version metadata
Further research: When making a correction, preserve the original event, before-and-after values and version, and distinguish revision of the conditions from a change in the clinical judgment as separate tasks.
Remaining uncertainty: Current judgment, relationships to related records, original axes and version metadata: this is the scope of the currently preserved record, without a new judgment of clinical efficacy, individual probability of success or safety.
Conditions for verification: Preserve the original C·50, axes, related document quality and historical relationship to 127, without repurposing grades/axes/scores for new judgments.
Why this condition is needed: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table.
Application exceptions: From 127, do not repurpose the B·60 judgment or pregnancy-nausea evidence, and do not open the original 127 file in this task.
Referenced methods: C01: Principles for clarifying the question in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are self-designed / C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules. Reason for applying this to the overall PMS score comparison: Preserving the original judgment does not issue an efficacy score or a checklist fulfillment rate for the new table. No official RoB2/GRADE assessment or clinical certification was performed.

Related sources

N37 · Are statements of insufficiency or uncertainty linked to the scope of preservation, reference date and conditions for updating?

Current findings: Record from the preservation-table review dated 2026-10-05: The original evidence reference date is 2026-09-15, and the review date for that work was 2026-10-05. Update conditions include dose, vitamer, hierarchy, scale, denominators, intervals, corrections, safety and recovery of the original location for the 80 mg/day record. The existing ZIP/calculation records were references only; no new search or effect calculation was performed.
Verification status: Met
Materials actually read: Summary reading: the specified original locations in the currently archived source summary were actually read. External originals and old separate copies were not read in this review.
Why unverified: The record of the scope verified and the update conditions was checked. This does not certify the completeness of the literature or the presence or absence of an effect.
Reason for missing information: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event
Required materials and conditions: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event
Materials to obtain first: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event
Further research: When new materials are permitted and become available, compare their identity, scope and version, and review only the observations and status of the relevant conditions again.
Remaining uncertainty: Dates, the actual preserved records of search/selection/calculation, and the original location of each update event: this is the scope of the currently preserved record, without a new judgment of clinical efficacy, individual probability of success or safety.
Conditions for verification: Record the original reference date, the date of the current review, the scope of what remains unverified and specific update events.
Why this condition is needed: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search.
Application exceptions: Do not label search, selection or calculation files in the old ZIP as materials actually read in this task.
Referenced methods: C09: M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and self-designed rules / E06: M08 Table 8.2.a, M04 §4.6.3; self-designed application. Reason for applying this to the overall PMS score comparison: This is needed to avoid overstating gaps in the current summary as absence of research worldwide, an effect of 0, or a current comprehensive search. No official RoB2/GRADE assessment or clinical certification was performed.

Related sources