{ "schema_version": "chamgap-public-evidence-check-1.0", "public_id": "v3096-main", "verdict_number": "3096", "title": "Vitamin B6: pyridoxine monotherapy × Reduced nausea severity in early pregnancy", "view_version": "1.0", "view_created_date": "2026-11-01", "criteria_version": "NGM-v3096-ORAL-PYRIDOXINE-EARLY-PREGNANCY-NAUSEA-1.1", "criteria_date": "2026-10-05", "review_date": "2026-10-05", "legacy_evidence_date": "2026-09-15", "review_scope": { "materials_read": "Archived Korean and English manuscripts and case-specific condition and application records", "clinical_papers_directly_read": false, "new_clinical_search": false, "limitation": "No new external clinical abstracts, full texts, registry records, or analysis plans were read. Historical access records are distinguished from the archived summaries read in this review. The original assessment, numerical values, and unverified items were preserved, with no new search, calculation, or reassessment.", "date_meaning": "This is the date on which the archived materials were checked, not the date of a search for the latest clinical literature." }, "claim_context": { "population": "Patients with nausea in early pregnancy; exact gestational weeks, diagnostic criteria, severity criteria, and inpatient status are unverified. The severe-nausea subgroup is kept separate from the overall group, and the findings are not generalized to hyperemesis gravidarum.", "intervention": "Vitamin B6 as pyridoxine alone · a single-ingredient oral preparation; hydrochloride identity, tablet/capsule form, release type, and excipients are unverified", "dose": "Main regimen: 25 mg every 8 hours; schedule-derived 75 mg/day; actual total intake and adherence are unverified. The supportive trial at 30 mg/day is separate.", "comparator": "Placebo; composition, common care, concomitant treatment, and rescue medication are unverified. Doxylamine combinations are not included.", "endpoint": "Between-group difference in nausea scores. The exact instrument, range, unit, assessment day, and endpoint hierarchy are unverified; not relabeled as a PUQE total.", "duration": "The retained record describes a short-term trial; exact treatment days, assessment day, and follow-up duration are unverified", "excluded_extensions": "PMS 3095, historical composite 127, doxylamine/ginger/prenatal combinations, other B6 forms/salts, PUQE, vomiting, hyperemesis gravidarum, fetal/birth events, and optimal dose/maintenance effects are separate." }, "requirements": [ { "item_id": "N01", "question_type": "Distinct claim", "question": "Which nausea comparison is addressed?", "needed": "Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to keep different pregnancy-related effects from being combined into a single efficacy claim.", "application_exception": "Vomiting, PUQE totals, hyperemesis gravidarum, PMS, and combination products are separate.", "criterion": "Link the exact original wording of the effect claim to the inclusion and exclusion boundaries.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed; M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the population, intervention, and endpoint boundaries in the manuscript and trial results separately.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "A single main claim of reduced nausea severity in early pregnancy was selected. The original claim_count=1, and there is no subclaims key.", "condition_status": "Met", "status_reason": "Confirming the identity of the question and demonstrating efficacy are separate matters.", "missingness": "Confirming the identity of the question and demonstrating efficacy are separate matters.", "uncertainty": "Confirming the identity of the question and demonstrating efficacy are separate matters.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Question: early pregnancy · oral pyridoxine monotherapy · 25 mg every 8 hours · placebo · nausea severity" }, { "item_id": "N02", "question_type": "Related assessments", "question": "Is this the same question as 127·3095?", "needed": "Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to keep related record numbers from being combined as the same study or the same efficacy claim.", "application_exception": "The related manuscripts and ZIP archives were not newly opened in this review.", "criterion": "Preserve the distinctions recorded in the current relationship object and the limitation that the underlying texts were not read.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are custom-designed; distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "If follow-up is authorized, compare the exact questions in the related authoritative versions to check for duplication.", "current_reports": [ "S01", "S03" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The current related_records distinguishes 127 as the historical PMS+pregnancy nausea composite and 3095 as a separate PMS-only claim.", "condition_status": "Met", "status_reason": "This is a reading of relationship metadata, not a review of the full related manuscripts.", "missingness": "This is a reading of relationship metadata, not a review of the full related manuscripts.", "uncertainty": "This is a reading of relationship metadata, not a review of the full related manuscripts.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Boundaries between the original composite assessment 127, PMS 3095, and the current nausea claim" }, { "item_id": "N03", "question_type": "Molecule and salt", "question": "Have the actual substance and salt been verified?", "needed": "Pyridoxine and the exact salt, active ingredient, and route", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to prevent findings for PLP or combination products from being repurposed under the name vitamin B6.", "application_exception": "Do not assume whether it is hydrochloride.", "criterion": "Record verified pyridoxine identity separately from the unverified salt.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link composition and quality documents to the results for the relevant trial arm.", "current_reports": [ "S01", "S07" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Recorded as oral pyridoxine monotherapy, but hydrochloride identity is unverified. It is not automatically equivalent to pyridoxal or PLP.", "condition_status": "Partly verified", "status_reason": "Verification of the exact salt remains outstanding.", "missingness": "Verification of the exact salt remains outstanding.", "uncertainty": "Verification of the exact salt remains outstanding.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Pyridoxine and the exact salt, active ingredient, and route" }, { "item_id": "N04", "question_type": "Product specifications", "question": "Are the manufacturing origin, manufacturer, and dosage form known?", "needed": "Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to prevent the single-ingredient dosage form in the question from being mistaken for actual product specifications.", "application_exception": "Do not assign the composition of a doxylamine product to the preparation being directly assessed.", "criterion": "Identify separately only the items verified in the directly studied preparation.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare batch and formulation documents with administration records to verify actual exposure.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Manufacturing origin, manufacturer, purity, batch, tablet/capsule, release type, and excipients are unverified within the retained materials.", "condition_status": "Unverified", "status_reason": "This does not mean that the information is absent from the original paper as a whole.", "missingness": "This does not mean that the information is absent from the original paper as a whole.", "uncertainty": "This does not mean that the information is absent from the original paper as a whole.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Manufacturing origin, brand, purity, batch, tablet/capsule, release type, and excipients" }, { "item_id": "N05", "question_type": "Dose and frequency", "question": "Are 25 mg every 8 hours and actual total exposure the same?", "needed": "Nominal dose, interval, actual intake, concurrent B6, and adherence", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to prevent schedule arithmetic from being treated as actual intake or a recommended dose.", "application_exception": "75 mg/day quotes the schedule arithmetic in the manuscript; it is not newly calculated.", "criterion": "Preserve the nominal regimen, historical arithmetic, and actual total exposure separately.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom-designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Obtain administration, medication-taking, and concurrent supplementation records by arm to verify total exposure.", "current_reports": [ "S01" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The main regimen of 25 mg every 8 hours and the original schedule arithmetic of 75 mg/day were preserved. The actual dose taken, total intake, and adherence are unverified.", "condition_status": "Partly verified", "status_reason": "Do not use 75 as the actual amount taken or a personally recommended dose.", "missingness": "Do not use 75 as the actual amount taken or a personally recommended dose.", "uncertainty": "Do not use 75 as the actual amount taken or a personally recommended dose.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Nominal dose, interval, actual intake, concurrent B6, and adherence" }, { "item_id": "N06", "question_type": "Duration and timing", "question": "Are the number of treatment days and the outcome assessment day known?", "needed": "Administration days, assessment day, and follow-up duration", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid imposing an arbitrary minimum long-term study duration on an acute-symptom question.", "application_exception": "Do not infer the exact number of days from the description “short-term” alone.", "criterion": "Record the difference between actual dates and durations and the level of detail in the retained description.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed; M08 Table 8.2.a, M04 §4.6.3; case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the timing in the dosing schedule, planned/actual assessment records, and results tables.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The retained description refers to a short-term trial, but the exact treatment days, assessment day, and follow-up duration are unverified.", "condition_status": "Unverified", "status_reason": "No new common duration threshold, such as 12 weeks, was set.", "missingness": "No new common duration threshold, such as 12 weeks, was set.", "uncertainty": "No new common duration threshold, such as 12 weeks, was set.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Administration days, assessment day, and follow-up duration" }, { "item_id": "N07", "question_type": "Population selection", "question": "How were patients in early pregnancy selected?", "needed": "Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to prevent the label “early pregnancy” from standing in for the actual recruitment criteria.", "application_exception": "Do not extend the population to include hyperemesis gravidarum.", "criterion": "Distinguish what has actually been verified about the population from items that could not be verified.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Obtain selection criteria, baseline tables, diagnostic criteria, and exclusion criteria, and compare them with the original question.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The population consists of patients with nausea in early pregnancy, but exact gestational weeks, diagnostic criteria, inpatient status, and inclusion/exclusion are unverified.", "condition_status": "Unverified", "status_reason": "The population dimension has not been removed; the remaining gap is detailed selection information.", "missingness": "The population dimension has not been removed; the remaining gap is detailed selection information.", "uncertainty": "The population dimension has not been removed; the remaining gap is detailed selection information.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Gestational weeks, diagnosis, age, hospitalization, exclusion, and representativeness" }, { "item_id": "N08", "question_type": "Baseline severity", "question": "Is the definition of the severe-nausea group known?", "needed": "Baseline scores, severity threshold, subgroup denominator, and selection criteria", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid extending improvement in the severe group to an effect in the overall group.", "application_exception": "Do not turn unverified baseline severity into a claim that all patients had severe nausea.", "criterion": "Explain the subgroup definition and actual results, and how they differ from those of the overall group.", "basis": "M03 §3.2.1; detailed population conditions are custom-designed; M03 §3.2.4, M15 §15.3.1–15.3.3; question-specific outcome adaptations are custom-designed; M03 §3.2.1–3.2.4; details of dose, duration, and effect modification are custom-designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the subgroup plan, baseline scores, and results tables by arm.", "current_reports": [ "S01" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The Sahakian summary describes improvement especially in the severe-nausea group. The severity threshold, denominator, and overall-group estimate are unverified.", "condition_status": "Partly verified", "status_reason": "Benefit for the overall group is not established from the description of the severe group alone.", "missingness": "Benefit for the overall group is not established from the description of the severe group alone.", "uncertainty": "Benefit for the overall group is not established from the description of the severe group alone.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Baseline scores, severity threshold, subgroup denominator, and selection criteria" }, { "item_id": "N09", "question_type": "Comparator composition", "question": "What was the actual placebo?", "needed": "Placebo composition, appearance, administration schedule, and common care by arm", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to prevent the label “placebo” from being used as proof that care was identical.", "application_exception": "Do not infer placebo composition when there is no record.", "criterion": "Separate the retained comparison type from the gap in actual composition details.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and adaptations for testing are custom-designed; M03 §3.2.3, M08 §8.2.2–8.2.3; case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link placebo, administration, and common-care documents to the original results.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Recorded as placebo-controlled, but details of composition, common care, and the schedules in both arms are unverified.", "condition_status": "Partly verified", "status_reason": "The comparator label and whether actual care was identical are separate matters.", "missingness": "The comparator label and whether actual care was identical are separate matters.", "uncertainty": "The comparator label and whether actual care was identical are separate matters.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Placebo composition, appearance, administration schedule, and common care by arm" }, { "item_id": "N10", "question_type": "Design", "question": "How much of the actual comparison design is retained?", "needed": "Actual parallel/crossover/cluster design, randomization, and blinding", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Because the label RCT alone does not establish that all allocation issues have been resolved.", "application_exception": "Do not assign crossover/cluster NA solely because the design is unverified.", "criterion": "Connect the summary-level description of the design that remains with the details that are unverified.", "basis": "M08 §8.1–8.2.3; case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare design information in Methods, allocation plans, and the paper’s results.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "S01/S02 are described in the archived summaries as randomized, double-blind, and placebo-controlled. Details on parallel/crossover/cluster design were not obtained.", "condition_status": "Partly verified", "status_reason": "This verifies the design record; it does not verify the full original Methods text.", "missingness": "This verifies the design record; it does not verify the full original Methods text.", "uncertainty": "This verifies the design record; it does not verify the full original Methods text.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Actual parallel/crossover/cluster design, randomization, and blinding" }, { "item_id": "N11", "question_type": "Allocation and baseline balance", "question": "Have allocation-sequence generation, concealment and baseline balance been verified?", "needed": "Sequence generation, concealment, baseline table and allocation implementation", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid certifying the adequacy of allocation on the basis of the word ‘randomized’ alone.", "application_exception": "No bias is established or additional deduction applied solely on the basis of unverified information.", "criterion": "Record the allocation details actually verified and the remaining gaps.", "basis": "M08 §8.1–8.2.3; case-specific application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Review allocation and outcome-specific differences using the protocol, Methods and baseline table.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The current summary does not provide details of sequence generation, concealment or baseline balance.", "condition_status": "Unverified", "status_reason": "These are unverified within the retained material; this does not establish non-reporting in the paper or bias.", "missingness": "These are unverified within the retained material; this does not establish non-reporting in the paper or bias.", "uncertainty": "These are unverified within the retained material; this does not establish non-reporting in the paper or bias.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Sequence generation, concealment, baseline table and allocation implementation" }, { "item_id": "N12", "question_type": "Adherence and rescue treatment", "question": "Were prenatal vitamins, rescue medication or concurrent B6 used alongside the intervention?", "needed": "Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid mistaking treatment differences for an effect of pyridoxine monotherapy.", "application_exception": "This does not require every change in both arms to be identical.", "criterion": "Distinguish the effect of interest from gaps in information on actual changes in each arm and how they were handled.", "basis": "M03 §3.2.3, M08 §8.2.2–8.2.3; local application; M08 §8.2.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link each arm’s medication, prenatal vitamin, rescue treatment and dosing records to the analysis plan.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Concomitant treatment, prenatal vitamins, rescue medication, adherence and arm-specific changes are unverified.", "condition_status": "Unverified", "status_reason": "The unverified status of concurrent B6 was not replaced with additional exposure of 0.", "missingness": "The unverified status of concurrent B6 was not replaced with additional exposure of 0.", "uncertainty": "The unverified status of concurrent B6 was not replaced with additional exposure of 0.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Concomitant treatment, rescue medication, adherence and discontinuations/changes by arm" }, { "item_id": "N13", "question_type": "Measurement scale", "question": "Is the nausea score a PUQE total score?", "needed": "Actual scale, range, units, direction and collection method", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid treating different symptom scales as the same outcome.", "application_exception": "PUQE use has not been verified, so the score is not relabeled as PUQE.", "criterion": "Separate nausea as the outcome from the unverified identity of the actual measurement instrument.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M03 §3.2.4; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the measurement instrument, items, timepoints and collection procedures with the original results tables.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The outcome was recorded as a nausea score, but the scale, range and units are unverified. It was not relabeled as a PUQE total score.", "condition_status": "Partly verified", "status_reason": "An unknown scale does not imply an effect of 0.", "missingness": "An unknown scale does not imply an effect of 0.", "uncertainty": "An unknown scale does not imply an effect of 0.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Actual scale, range, units, direction and collection method" }, { "item_id": "N14", "question_type": "Blinding in measurement", "question": "Are measurement conditions for assessors and patients the same across arms?", "needed": "Outcome collection, blinding in assessment and measurement procedures by arm", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to distinguish differences in collecting subjective symptoms from actual differences in effect.", "application_exception": "The double-blind label and outcome-specific details of blinding are separate.", "criterion": "Retain the actual conditions of measurement for the selected nausea outcome and the aspects that cannot be verified.", "basis": "M08 Table 8.2.a, M03 §3.2.4; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare assessment guidance, recording methods and records verifying blinding.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The description as double-blind is retained, but nausea measurement procedures, the assessors’ actual blinding and differences in collection between arms are unverified.", "condition_status": "Unverified", "status_reason": "It was not established that a measurement problem occurred.", "missingness": "It was not established that a measurement problem occurred.", "uncertainty": "It was not established that a measurement problem occurred.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Outcome collection, blinding in assessment and measurement procedures by arm" }, { "item_id": "N15", "question_type": "Endpoint hierarchy", "question": "Was nausea a prespecified primary (1st) endpoint?", "needed": "Registration, protocol, endpoint/timepoint hierarchy and reasons for changes", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid retrospectively treating this page’s question as the original trial’s primary (1st) endpoint.", "application_exception": "Failure to acquire a registration record is not converted into confirmation of non-registration or selective reporting.", "criterion": "Distinguish plans that could not be cross-checked from the known nausea findings.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M04 §4.6.3; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the protocol, registration versions and analysis plan with the original results tables.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The selected question concerns nausea scores, but the original trial’s endpoint hierarchy, prespecified timepoints and reasons for changes are unverified.", "condition_status": "Unverified", "status_reason": "Defining the current question does not mean that registration review is complete.", "missingness": "Defining the current question does not mean that registration review is complete.", "uncertainty": "Defining the current question does not mean that registration review is complete.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Registration, protocol, endpoint/timepoint hierarchy and reasons for changes" }, { "item_id": "N16", "question_type": "Effect definition", "question": "Can between-group differences, within-group differences and adjusted effects be distinguished?", "needed": "Analysis population, baseline/end/change values, adjustment and ITT/PP", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid converting a description of improvement into a formal placebo-adjusted effect.", "application_exception": "Do not assume ITT when the analysis is unclear.", "criterion": "Preserve the distinction between a formal contrast and a qualitative description.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 §8.2.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link the actual analysis tables, denominators and analysis plan to the selected nausea outcome.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The formal overall between-group effect, definitions of baseline/change/end values, analysis population, adjustment and ITT/PP are unverified.", "condition_status": "Unverified", "status_reason": "Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.", "missingness": "Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.", "uncertainty": "Improvement described especially in the severe group was not used on its own to reconstruct a formal between-group effect.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Analysis population, baseline/end/change values, adjustment and ITT/PP" }, { "item_id": "N17", "question_type": "Effect and interval", "question": "Are the overall-group effect size, CI and P value known?", "needed": "Between-group estimate, dispersion, denominator, P value and CI", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid converting an unverified effect into statistical non-significance or no effect.", "application_exception": "Retain the preserved signal without calculating a new effect.", "criterion": "Specify which aspects of the formal overall-group effect cannot be verified.", "basis": "M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M15 §15.3.1–15.3.3; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Review the effect, interval, denominator and units in the original Results and analysis tables.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The formal overall-group effect size, CI, P value and dispersion could not be verified from the currently retained summaries.", "condition_status": "Unverified", "status_reason": "This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.", "missingness": "This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.", "uncertainty": "This is neither a claim that the original paper contains no numbers nor proof of an effect of 0.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Between-group estimate, dispersion, denominator, P value and CI" }, { "item_id": "N18", "question_type": "Main trial denominator", "question": "What is the figure of 59 people a denominator for?", "needed": "Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid using a sample label as the actual denominator for the nausea analysis.", "application_exception": "Do not split 59 into arm-specific or event denominators for calculations.", "criterion": "Distinguish the verified sample label from the unverified stage/arm-specific denominators.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Obtain CONSORT records, original tables and analysis-population records, and link participant counts at each stage.", "current_reports": [ "S01" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Sahakian is recorded as having 59 participants. The stage and arm-specific analysis denominators are unverified.", "condition_status": "Partly verified", "status_reason": "59 is a retained number, not a verified arm-specific analysis n.", "missingness": "59 is a retained number, not a verified arm-specific analysis n.", "uncertainty": "59 is a retained number, not a verified arm-specific analysis n.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Sahakian: numbers allocated, completing and analyzed by arm, and numbers for each outcome" }, { "item_id": "N19", "question_type": "Supportive trial denominator", "question": "Is the figure of 342 people a denominator for the same regimen?", "needed": "Vutyavanich: participant stages by arm, numbers analyzed and dose", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid combining the sample at a different dose with the main trial denominator or treating it as independent replication.", "application_exception": "Do not add 342 and 59 together.", "criterion": "Record the participant counts and the differences in regimens and study families separately.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare the original supportive-trial results tables with recruitment, allocation, completion and analysis records.", "current_reports": [ "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Vutyavanich is recorded as having 342 participants at 30 mg/day. The participant stage and arm-specific analysis denominators are unverified, and the regimen differs from the main regimen of 25 mg every 8 hours.", "condition_status": "Partly verified", "status_reason": "The large sample label was not treated as evidence of precision for the directly assessed regimen.", "missingness": "The large sample label was not treated as evidence of precision for the directly assessed regimen.", "uncertainty": "The large sample label was not treated as evidence of precision for the directly assessed regimen.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Vutyavanich: participant stages by arm, numbers analyzed and dose" }, { "item_id": "N20", "question_type": "Missing data and attrition", "question": "What were the dropouts, missing data and discontinuations, and how were they handled?", "needed": "Attrition, missing data, reasons and outcome-specific handling by arm", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid treating an unknown analysis denominator as absence of attrition.", "application_exception": "Do not calculate dropout rates from the retained participant counts alone.", "criterion": "Separate actual observed losses from the scope of what cannot be verified.", "basis": "M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; design-specific adaptation is locally designed; M08 §8.2.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare participant flow, missingness in the original data, reasons for discontinuation and analysis methods.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The manuscript’s sample records of 59/342 alone cannot establish arm-specific dropout, missing data, discontinuation or handling methods.", "condition_status": "Unverified", "status_reason": "Do not assume 0 missing data or complete follow-up.", "missingness": "Do not assume 0 missing data or complete follow-up.", "uncertainty": "Do not assume 0 missing data or complete follow-up.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Attrition, missing data, reasons and outcome-specific handling by arm" }, { "item_id": "N21", "question_type": "Replication and dose differences", "question": "Does a trial at a different dose replicate the same regimen?", "needed": "Unique study families, ingredient, dose, scale, duration and population", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid upgrading a positive description at a different dose to independent replication of the same regimen.", "application_exception": "Retain the supportive findings and state the boundaries.", "criterion": "Explain the actual similarities/differences between the two study families and what remains unverified.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application; M04 §4.6.1–4.6.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Compare formulation, population, measurement and analysis across study families to verify the scope of replication.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "TF-SAH-1991 and TF-VUT-1995 were retained separately. The main regimen is 25 mg every 8 hours, and the supportive regimen is 30 mg/day; they are not combined as same-dose replication.", "condition_status": "Met", "status_reason": "This verifies the distinction between study families; it does not verify independent funding or use of the same scale.", "missingness": "This verifies the distinction between study families; it does not verify independent funding or use of the same scale.", "uncertainty": "This verifies the distinction between study families; it does not verify independent funding or use of the same scale.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Unique study families, ingredient, dose, scale, duration and population" }, { "item_id": "N22", "question_type": "Contrary and other findings", "question": "Were the vomiting findings the same as those for nausea?", "needed": "Separate findings, analyses and timepoints for nausea and vomiting", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid deleting less consistent vomiting findings or turning them into a nausea effect.", "application_exception": "Vomiting is not included as a required endpoint for the selected nausea question.", "criterion": "Assign positive/inconsistent signals from different findings to their respective endpoints.", "basis": "M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is locally designed; M03 §3.2.4, M15 §15.3.1–15.3.3; adaptation of outcomes to each question is locally designed; M04 §4.6.1–4.6.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Retain the original nausea and vomiting results tables separately, and compare them with findings for the original question.", "current_reports": [ "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Both the supportive trial’s description of nausea improvement and its less consistent vomiting findings were retained. Vomiting frequency is separate from nausea scores.", "condition_status": "Met", "status_reason": "The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.", "missingness": "The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.", "uncertainty": "The qualitative vomiting record was not reconstructed into numerical findings of statistical significance/non-significance.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Separate findings, analyses and timepoints for nausea and vomiting" }, { "item_id": "N23", "question_type": "Clinical importance", "question": "What degree of reduction is important?", "needed": "Justified scale-specific important differences, between-group CI, and patient interpretation", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid declaring a definite clinical benefit from an improvement signal alone.", "application_exception": "Do not create arbitrary score thresholds, minimum participant counts, or minimum numbers of studies.", "criterion": "Explain the verified criteria and intervals, or why interpretation is not possible.", "basis": "M15 §15.3.1–15.3.3; internally applied", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link scale-validation and patient-importance data to the actual effect interval.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The exact scale, effect interval, and applicable clinically important difference are unverified.", "condition_status": "Unverified", "status_reason": "Retain the qualitative improvement without establishing the magnitude or importance of the benefit.", "missingness": "Retain the qualitative improvement without establishing the magnitude or importance of the benefit.", "uncertainty": "Retain the qualitative improvement without establishing the magnitude or importance of the benefit.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Justified scale-specific important differences, between-group CI, and patient interpretation" }, { "item_id": "N24", "question_type": "Funding and independence", "question": "Have funding, product provision, and conflict-of-interest records for the two trials actually been verified?", "needed": "Funding, product provision, author employment, COI, and study families", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid turning the original axis treatment of unverified funding into actual industry support or independent funding.", "application_exception": "Do not automatically discard results because of interests involved.", "criterion": "Verify funding, product provision, author employment, and COI for each trial by linking them to locations in the actual records. Leave unverified items unverified and distinguish them from the explanation of the original I1 scoring policy.", "basis": "Chamgap’s own conditions for independence and attribution. The official methods sections used in this pilot do not validate all these detailed items.", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Cross-check the papers’ Funding/COI statements, product-supply records, and institutional/study-family records.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Funding, product provision, and COI for the two trials are unverified. The original I1 applies the rule for unverified funding; it does not confirm manufacturer support.", "condition_status": "Unverified", "status_reason": "No new independence assessment or revision of the original axes was performed.", "missingness": "No new independence assessment or revision of the original axes was performed.", "uncertainty": "No new independence assessment or revision of the original axes was performed.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Funding, product provision, author employment, COI, and study families" }, { "item_id": "N25", "question_type": "Material types and guidelines", "question": "Have the actual version, original recommendation text, current status, and links to supporting trials of the ACOG guideline been verified?", "needed": "Roles, locations, and versions of the guideline, original trials, and archived summaries", "role": "Supplementary; essential for guideline interpretation", "role_reason": "Needed to avoid treating recommendations as a new effect estimate or grading basis for the selected regimen.", "application_exception": "The current guideline full text and current status were not read or reviewed in this work.", "criterion": "Cross-check the guideline’s bibliographic details, version, original recommendations, current status, and links to supporting trials against the locations actually verified. Separate the retained 2018 contextual description from the material not read or cross-checked in this work, and do not use it as direct effect evidence or a new grading basis.", "basis": "M04 §4.5–4.6 principles for collecting/selecting materials; the separation of access from reading and the hyperlink contract are internally designed; M04 §4.5, §4.6.3; limits on the current material conversion follow the user-defined scope and internal design; M04 §4.6.1–4.6.2, M15 §15.3.1; internally applied", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "If follow-up is authorized, link the guideline’s original text and version, and the trials supporting its recommendations, separately.", "current_reports": [ "S03" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "S03 ACOG 2018 is contextual material from an archived summary describing historical recommendations. It was not used as direct effect evidence or a new grading basis.", "condition_status": "Partly verified", "status_reason": "The exact current version, full original recommendation text, and status are unverified.", "missingness": "The exact current version, full original recommendation text, and status are unverified.", "uncertainty": "The exact current version, full original recommendation text, and status are unverified.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Roles, locations, and versions of the guideline, original trials, and archived summaries" }, { "item_id": "N26", "question_type": "Direct harms", "question": "Are the denominators for maternal and fetal adverse events known?", "needed": "Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid treating the existence of efficacy summaries as verification of safety in pregnancy.", "application_exception": "Do not convert general B6 safety records into fetal event counts for the trials.", "criterion": "Distinguish the applicability of direct pregnancy-harm records from that of general harm records.", "basis": "M19 §19.1.2–19.2.4; internally applied; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Obtain the original trials’ safety tables and arm-level follow-up, exposure, and discontinuation records.", "current_reports": [ "S01", "S02", "S04", "S05" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The retained NVP trial summaries alone cannot verify maternal/fetal AE, SAE, discontinuations, or long-term safety.", "condition_status": "Unverified", "status_reason": "The current unverified status does not mean 0 harms or established safety.", "missingness": "The current unverified status does not mean 0 harms or established safety.", "uncertainty": "The current unverified status does not mean 0 harms or established safety.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Maternal/fetal AE, SAE, discontinuations, ascertainment, duration, and denominators by arm" }, { "item_id": "N27", "question_type": "General B6 harms", "question": "What is the scope of applicability of the neuropathy warning?", "needed": "General neuropathy data, exposure, populations, recovery, and applicability to pregnancy", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid converting a general warning into a risk rate for short-term pregnancy trials.", "application_exception": "Retain the harm signal without newly calculating incidence in pregnancy.", "criterion": "Distinguish the claims in the currently retained official extraction from the gaps in the pregnancy comparison.", "basis": "M19 §19.1.2–19.2.4; internally applied; M03 §3.2.1; detailed population conditions are internally designed; M08 Table 8.2.a, M15 §15.3, M19 §19.1.2–19.2.4; adaptations by study design are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Review individual exposure, neurological symptoms, recovery follow-up data, and applicability to pregnant populations.", "current_reports": [ "S04", "S05" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "General B6 safety records describe neuropathy below 50 mg/day and do not guarantee recovery. These are not arm-level risk rates from NVP trials.", "condition_status": "Partly verified", "status_reason": "Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.", "missingness": "Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.", "uncertainty": "Exact denominators, durations, and causal risks by exposure in pregnancy are unverified.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "General neuropathy data, exposure, populations, recovery, and applicability to pregnancy" }, { "item_id": "N28", "question_type": "Regulation and upper limits", "question": "Have the versions, effective dates, and applicability of official upper-limit, warning, and regulatory records been verified?", "needed": "Nutritional upper limits, warning thresholds, policy effective dates, and intended uses", "role": "Supplementary; essential for policy and safety interpretation", "role_reason": "Needed to avoid turning official policy numbers into recommended treatment doses for pregnancy nausea.", "application_exception": "Do not describe the regulation scheduled for 2027-06-01 as currently in force.", "criterion": "Link each official document’s version, publication/effective dates, applicable population, and scope to the locations actually verified. Separate the retained upper limits, warnings, and scheduled changes at the original cutoff from what has not been cross-checked in this work, and distinguish them from treatment doses for pregnancy nausea.", "basis": "M04 §4.5, §4.6.3; limits on the current material conversion follow the user-defined scope and internal design; M19 §19.1.2–19.2.4; internally applied", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "During an authorized update, separately verify the actual policy versions, effective dates, and applicability.", "current_reports": [ "S04", "S06" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Retain the EFSA adult chronic total-intake UL of 12 mg/day, the TGA warning above 10 mg/day, and the change for the range above 50 mg/day~200 mg/day scheduled for 2027-06-01 as records at the original cutoff of 2026-09-15.", "condition_status": "Partly verified", "status_reason": "Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.", "missingness": "Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.", "uncertainty": "Current policy rechecks: 0. These numbers are not personal treatment doses in pregnancy.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Nutritional upper limits, warning thresholds, policy effective dates, and intended uses" }, { "item_id": "N29", "question_type": "Separating harms by preparation", "question": "Is doxylamine-related drowsiness being attributed to B6 alone?", "needed": "Ingredient-specific harms and comparisons for single-ingredient and combination preparations", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid attributing another ingredient’s adverse effects to pyridoxine alone.", "application_exception": "The efficacy and harms of doxylamine combinations are separate.", "criterion": "Explain the preparation/ingredient boundaries and limits on the applicability of the records.", "basis": "M03 §3.2.2–3.2.3; reverse-direction labeling and test adaptations are internally designed; M19 §19.1.2–19.2.4; internally applied", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link the combination’s composition and each ingredient’s safety records to the actual exposure separately.", "current_reports": [ "S03", "S07", "S08" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Doxylamine drowsiness information was not transferred to adverse effects of B6 alone. Ginger and prenatal multivitamin results were also kept separate from monotherapy evidence.", "condition_status": "Met", "status_reason": "This does not establish that B6 alone has no harms.", "missingness": "This does not establish that B6 alone has no harms.", "uncertainty": "This does not establish that B6 alone has no harms.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Ingredient-specific harms and comparisons for single-ingredient and combination preparations" }, { "item_id": "N30", "question_type": "Symptoms and events", "question": "Are nausea results being used to answer questions about fetal/birth events as well?", "needed": "Separate results for nausea scores and for hospitalization, birth, and fetal clinical events", "role": "Supplementary (essential only when extending to separate events)", "role_reason": "Needed to avoid extending symptom reduction to improvement in separate clinical events.", "application_exception": "Do not impose separate event trials as additional mandatory conditions for the narrow nausea question.", "criterion": "State the boundary between the selected symptom question and questions about other events.", "basis": "M03 §3.2.4; internally defined boundary for extensions", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Review event-specific definitions, denominators, and follow-up separately only when addressing an extension to events.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The efficacy question in this table concerns nausea severity; it does not also assess hyperemesis gravidarum treatment, hospitalization, or improvement in fetal/birth events.", "condition_status": "Not applicable", "status_reason": "Gaps in maternal and fetal safety information remain in the separate harm items.", "missingness": "Gaps in maternal and fetal safety information remain in the separate harm items.", "uncertainty": "Gaps in maternal and fetal safety information remain in the separate harm items.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Separate results for nausea scores and for hospitalization, birth, and fetal clinical events" }, { "item_id": "N31", "question_type": "Optimal dose", "question": "Which of the two doses is better?", "needed": "Direct dose comparisons, exposure, the same scale, and intervals", "role": "Supplementary (essential only when extending to the optimal dose)", "role_reason": "Needed to avoid converting summaries from separate trials into a comparison of dose effects.", "application_exception": "Determining the optimal dose is not an additional requirement for the current narrow question about the main regimen.", "criterion": "Distinguish the lack of verified direct dose comparisons from the attribution of supportive results.", "basis": "M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "When adding an optimal-dose question, separately design direct dose comparisons in the same population.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The 25 mg every 8 hours and 30 mg/day records belong to different study families and are not combined as direct dose-comparison or optimal-dose evidence.", "condition_status": "Not applicable", "status_reason": "A separate dose-related extension was not imposed on the current efficacy conditions.", "missingness": "A separate dose-related extension was not imposed on the current efficacy conditions.", "uncertainty": "A separate dose-related extension was not imposed on the current efficacy conditions.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Direct dose comparisons, exposure, the same scale, and intervals" }, { "item_id": "N32", "question_type": "Persistence and recovery", "question": "Does the assessment also address maintenance of effect after discontinuation?", "needed": "Separate results for discontinuation, maintenance, and long-term follow-up", "role": "Supplementary (essential only when extending to maintenance of effect)", "role_reason": "Needed to avoid extending short-term symptom results to maintenance or prevention of recurrence.", "application_exception": "Do not use a minimum long-term follow-up requirement as an arbitrary threshold for the current acute comparison.", "criterion": "Record the separate boundary between the selected acute outcome and maintenance of effect.", "basis": "M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "When adding a maintenance question, separately track post-discontinuation assessments, concurrent care, and recurrence.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The current short-term nausea comparison does not establish maintenance of effect after discontinuation or prevention of recurrence.", "condition_status": "Not applicable", "status_reason": "Gaps in long-term safety were retained separately from direct harms.", "missingness": "Gaps in long-term safety were retained separately from direct harms.", "uncertainty": "Gaps in long-term safety were retained separately from direct harms.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Separate results for discontinuation, maintenance, and long-term follow-up" }, { "item_id": "N33", "question_type": "Subgroup planning", "question": "Was effect modification by severe nausea planned in advance?", "needed": "Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid using subgroup improvement as the main effect for all patients.", "application_exception": "Retain the subgroup description and its exploratory/planned status.", "criterion": "Distinguish the levels of verification for prespecified definitions and formal interactions.", "basis": "M08 Table 8.2.a, M04 §4.6.3; internally applied; M03 §3.2.1–3.2.4; details on dose, persistence, and effect modification are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Cross-check the protocol and analysis plan against severity-specific results/interactions.", "current_reports": [ "S01" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The severe-nausea subgroup criteria, prespecification, interactions, and separate CI are unverified.", "condition_status": "Unverified", "status_reason": "Positive subgroup descriptions were not generalized to the whole-group effect.", "missingness": "Positive subgroup descriptions were not generalized to the whole-group effect.", "uncertainty": "Positive subgroup descriptions were not generalized to the whole-group effect.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Prespecified severe-subgroup definitions, interactions, separate estimates, and intervals" }, { "item_id": "N34", "question_type": "Preserving original values", "question": "Were C46 and the original axes automatically carried over to the new table?", "needed": "Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "Needed to avoid turning citation of the original assessment into a new efficacy score or condition-fulfillment rate.", "application_exception": "The original B1, I1, EX, and CX reflect historical policy, not new calculations in this table.", "criterion": "Preserve the original C46, axes and limitations exactly, without creating new judgment values.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; M04 §4.6.3, M15 §15.3.1–15.3.3; separation of statuses is internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "When a separately authorized change arises, review it while preserving the original judgment, materials, condition version and affected fields.", "current_reports": [ "S01", "S02" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The original C·46 and B/P/R1/I1/EX/B1/CX, with no_human_study=false, were preserved. The original explanation of the signal, unverified effect size, unverified funding and sample limitation of 59 was also retained.", "condition_status": "Met", "status_reason": "The grade is not used as a condition status, an individual probability of success or a safety assessment.", "missingness": "The grade is not used as a condition status, an individual probability of success or a safety assessment.", "uncertainty": "The grade is not used as a condition status, an individual probability of success or a safety assessment.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Original grade/score, 7 axes, gates, and their meaning, distinguished from the new conditions" }, { "item_id": "N35", "question_type": "Reports/families", "question": "Do 8 bibliographic records represent 8 clinical trials?", "needed": "Links among reports, the two trial families, the guideline and official safety information", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "This is needed to avoid turning a bibliographic count into a count of independent pregnancy trials.", "application_exception": "Do not assume independence and pool included trials/participants.", "criterion": "Record each report’s material type, family, endpoint and limitations concerning overlap.", "basis": "Distinction between studies and reports in M04 §4.6.1–4.6.2; cohort/outcome linkage is a local application; M04 §4.6.1–4.6.2, M15 §15.3.1; local application", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "Link report/trial/result identities and leave unknown relationships unknown.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "S01/S02 are two trial families with different regimens. S03 is retained as guideline context, and S04–08 as general official safety/nutrition and drug information; they are not counted as 8 trials.", "condition_status": "Met", "status_reason": "No independent-participant total or total number of human studies was calculated.", "missingness": "No independent-participant total or total number of human studies was calculated.", "uncertainty": "No independent-participant total or total number of human studies was calculated.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Links among reports, the two trial families, the guideline and official safety information" }, { "item_id": "N36", "question_type": "Current reading", "question": "Have actual acquisition, reading and original bytes of the archived summaries and linked original materials been verified?", "needed": "Current archived-summary locations/values/SHA, original-material types, historical access and current access actions", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "This is needed to avoid turning a link or a historical access level into a full-text reading in this task.", "application_exception": "External originals/separate legacy and safety-extraction source files/ZIPs were not opened in this task.", "criterion": "For each material, record the exact location, value and SHA of the currently retained archived summary and its actual reading, together with the verified scope of acquisition, reading and file SHA for the linked original material. Do not inherit a historical material-type declaration as current source-file acquisition or full-text reading; leave unverified aspects unresolved.", "basis": "Data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink specification are internally designed", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "When subsequent acquisition is authorized, record the actual file/location/date/SHA as a new access event.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The currently retained archived-summary text, bibliographic information and linked summaries were actually read. provided_secondary_summary and provided_official_source_extraction are historical material-type records in the manuscript; external full texts have not been read in this task.", "condition_status": "Partly verified", "status_reason": "Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.", "missingness": "Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.", "uncertainty": "Current acquisition of separate source files/original bytes and original Methods/results tables is unverified.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Current archived-summary locations/values/SHA, original-material types, historical access and current access actions" }, { "item_id": "N37", "question_type": "Search/reference date", "question": "Is this the latest conclusion from the entire current literature?", "needed": "Evidence reference date, actual review date and scope of searches/corrections/retractions", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "This is needed to avoid turning the absence of a new search into 0 studies or confirmation of current recommendations.", "application_exception": "The original review date of 2026-09-15 is not an access date for this task.", "criterion": "Record the reference point of the retained materials separately from the time of review for the current conversion.", "basis": "M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and internal design", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "During an authorized update, add the actual search queries, original materials and verification of publication status as new events.", "current_reports": [ "S01", "S02", "S03" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "The evidence reference date of 2026-09-15 was preserved. This conversion was limited to the currently archived summaries, without a new clinical search or rechecking guidelines/registrations/corrections/retractions.", "condition_status": "Met", "status_reason": "Statements about the presence or absence of materials are limited to this preserved scope.", "missingness": "Statements about the presence or absence of materials are limited to this preserved scope.", "uncertainty": "Statements about the presence or absence of materials are limited to this preserved scope.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Evidence reference date, actual review date and scope of searches/corrections/retractions" }, { "item_id": "N38", "question_type": "Update conditions", "question": "Which items should change when which materials are acquired?", "needed": "Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections", "role": "Required (selected comparison for nausea in early pregnancy)", "role_reason": "This is needed to avoid treating the addition of a material as automatic confirmation of an effect or revision of the condition version.", "application_exception": "Do not modify the original judgment, related manuscripts or the site while preparing this table.", "criterion": "Keep the original update triggers, linked conditions/materials and preservation of historical original text distinct.", "basis": "Question-clarification principles in M03 §3.1, §3.2.1–3.2.4; detailed separation rules are internally designed; data collection/selection principles in M04 §4.5–4.6; separation of access from reading and the hyperlink specification are internally designed; M04 §4.5, §4.6.3; limits on the current conversion of materials follow the user-defined scope and internal design", "condition_origin": "Development conditions individually designed with knowledge of the actual retained materials; not blinded, clinically preregistered, or officially certified", "proposed_research": "When separately authorized, preserve the complete original text before the change and record additions of materials, revisions of conditions and changes to the judgment separately.", "current_reports": [ "S01", "S02", "S03", "S04", "S05", "S06", "S07", "S08" ], "existence": "Retained archived summaries/bibliographic and historical records exist; current external lookups: 0", "acquired_read": "The exact retained archived summaries were actually read; linked original materials/external full texts were not read in this review", "observation": "Record from the preservation-table review dated 2026-10-05: The original revision_triggers for result recovery, preparation/population corrections, plans/denominators, maternal/fetal safety, retractions/errors and guidelines/actual effective dates were linked to the corresponding gaps.", "condition_status": "Met", "status_reason": "No subsequent research was performed, and no new score/judgment was created and applied.", "missingness": "No subsequent research was performed, and no new score/judgment was created and applied.", "uncertainty": "No subsequent research was performed, and no new score/judgment was created and applied.", "review_date": "2026-10-05", "reading_status": "Original text not read · archived summary read", "additional_material": "Identity/version/location of original results, exact preparation, plans/denominators, safety information and corrections" } ], "reports": [ { "report_id": "S01", "title": "Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study", "url": "https://pubmed.ncbi.nlm.nih.gov/2047064/", "report_type": "Retained secondary (2nd) summary of the main dose-matched trial", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "TF-SAH-1991", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "59 participants; 25 mg every 8 hours; improvement described especially in severe nausea; formal overall-group effect/CI/per-arm analysis n unverified.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S01-M1", "url": null, "parent_url": null }, { "material_type": "PubMed original-trial index/abstract entry point", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S01-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/2047064/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/2047064/" } ] }, { "report_id": "S02", "title": "Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial", "url": "https://pubmed.ncbi.nlm.nih.gov/7573262/", "report_type": "Retained secondary (2nd) summary of the supportive trial at a different dose", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "TF-VUT-1995", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "342 participants; 30 mg/day; nausea improvement/less consistent vomiting findings; not same-dose replication; formal effect/CI/per-arm analysis n unverified.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S02-M1", "url": null, "parent_url": null }, { "material_type": "PubMed original-trial index/abstract entry point", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Exact Methods/Results/table location not recovered; no primary numerical outcome quoted. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S02-M2", "url": "https://pubmed.ncbi.nlm.nih.gov/7573262/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://pubmed.ncbi.nlm.nih.gov/7573262/" } ] }, { "report_id": "S03", "title": "ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy", "url": "https://doi.org/10.1097/AOG.0000000000002456", "report_type": "Retained secondary (2nd) summary providing guideline context", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "CONTEXT-ACOG-189-2018", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "Context describing historical recommendations. Not a formal direct pyridoxine effect or evidence for a new grade.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Recommendations described in the historical record; current full text and current status not checked. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S03-M1", "url": null, "parent_url": null }, { "material_type": "Guideline DOI entry point", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_secondary_summary. Recommendations described in the historical record; current full text and current status not checked. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S03-M2", "url": "https://doi.org/10.1097/AOG.0000000000002456", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://doi.org/10.1097/AOG.0000000000002456" } ] }, { "report_id": "S04", "title": "TGA 2026. Medicines containing vitamin B6 (pyridoxine, pyridoxal or pyridoxamine)", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine", "report_type": "Retained record of an extraction of general official safety information", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "OFFICIAL-TGA-SCHEDULING-2026", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "Neuropathy/policy record. Distinguish the >10 warning and the >50~200 change scheduled for 2027-06-01, which was future at the original reference date. Not a risk rate in pregnancy.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S04-M1", "url": null, "parent_url": null }, { "material_type": "Entry point for the official TGA safety/regulatory document", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Published 19 February 2026, updated 7 April 2026; scheduling and neuropathy sections. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S04-M2", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.tga.gov.au/news/safety-updates/medicines-containing-vitamin-b6-pyridoxine-pyridoxal-or-pyridoxamine" } ] }, { "report_id": "S05", "title": "TGA 2026. Are you unknowingly taking too much vitamin B6?", "url": "https://www.tga.gov.au/news/blog/are-you-unknowingly-taking-too-much-vitamin-b6", "report_type": "Retained record of an extraction of general official safety information", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "OFFICIAL-TGA-CUMULATIVE-2026", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "Records of neuropathy below 50 mg/day, cumulative intake and recovery not guaranteed. Denominators/causal risks in pregnancy trials are unverified.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S05-M1", "url": null, "parent_url": null }, { "material_type": "Entry point for the official TGA safety document", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. 4 March 2026; peripheral neuropathy, cumulative intake, irreversible injury and stopping advice. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S05-M2", "url": "https://www.tga.gov.au/news/blog/are-you-unknowingly-taking-too-much-vitamin-b6", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.tga.gov.au/news/blog/are-you-unknowingly-taking-too-much-vitamin-b6" } ] }, { "report_id": "S06", "title": "EFSA 2023. Scientific opinion on the tolerable upper intake level for vitamin B6", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/8006", "report_type": "Retained record of an extraction on the official nutritional upper intake limit", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "OFFICIAL-EFSA-UL-2023", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "The adult chronic total-intake UL of 12 mg/day is not a treatment dose for pregnancy nausea.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Abstract; Conclusions, adult UL derivation. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S06-M1", "url": null, "parent_url": null }, { "material_type": "Entry point for the original official EFSA opinion", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Abstract; Conclusions, adult UL derivation. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S06-M2", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/8006", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://www.efsa.europa.eu/en/efsajournal/pub/8006" } ] }, { "report_id": "S07", "title": "NIH ODS. Vitamin B6: Fact Sheet for Health Professionals", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/", "report_type": "Retained record of an extraction of official nutrition/general safety information", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "OFFICIAL-NIH-B6", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "General context on forms, nutritional intake and harms of excess. Not a monotherapy efficacy comparison result in pregnancy.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S07-M1", "url": null, "parent_url": null }, { "material_type": "Entry point for official NIH ODS information", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Vitamin forms; Recommended Intakes; Health Risks from Excessive Vitamin B6. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S07-M2", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/" } ] }, { "report_id": "S08", "title": "MedlinePlus. Pyridoxine drug information", "url": "https://medlineplus.gov/druginfo/meds/a682587.html", "report_type": "Retained record of an extraction of official drug information", "existence": "This refers to archived bibliographic information and historical records; the current external response has not been verified.", "acquired_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.", "study_family": "OFFICIAL-MEDLINE-PYRIDOXINE", "independent_replication": "Bibliographic records 8≠8 trials. Separate the two regimen families, guideline and general official safety information; participant pooling/independence certification: 0", "observed_result": "Retained context on special precautions and side effects; original revised 2017-08-15, current lookups 0. Research amounts are not converted into personal doses.", "result_level": "This is content recorded in the archived manuscript, not the result of a new comparison with current external original materials.", "source_evidence_date": "2026-09-15", "materials": [ { "material_type": "Retained archived-summary bibliographic information and linked summaries/historical records", "public_status": "Retained locally", "access_status": "Acquired", "acquired": true, "actually_read": "Summary read", "as_of": "2026-11-01", "qualification": "Exact location and value/SHA, not bytes of the original clinical full text. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Special precautions; side effects; revised 15 August 2017. This record does not mean that the external original material was acquired or its full text read in this task. What was actually read comprises the exact location and value of the archived summary, not the bytes of the original clinical text.", "material_id": "S08-M1", "url": null, "parent_url": null }, { "material_type": "MedlinePlus drug-information entry point", "public_status": "Unverified (0 current external lookups)", "access_status": "Access not attempted", "acquired": false, "actually_read": "Not read", "as_of": "2026-11-01", "qualification": "Distinguish the external entry point from what was read in this task. Preserve the historical material type and original location without assigning successful access in this task. The historical access date for each material is unverified. The archived manuscript’s review date, 2026-09-15, is not the access date of the original source file. Historical material-type record: provided_official_source_extraction. Special precautions; side effects; revised 15 August 2017. This record does not mean that the external original material was acquired or its full text read in this task.", "material_id": "S08-M2", "url": "https://medlineplus.gov/druginfo/meds/a682587.html", "parent_url": null } ], "links": [ { "label": "Source", "url": "https://medlineplus.gov/druginfo/meds/a682587.html" } ] } ], "method_sources": [ { "id": "M03", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-03", "section": "§3.1, §3.2.1–3.2.3, MECIR C5/C7/C13", "official_principle": "Clearly record the question, eligibility conditions and reasons for changes, and distinguish variations of the intervention.", "review_level": "Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool" }, { "id": "M04", "version": "Cochrane Handbook 6.5.1 (2025), chapter updated 2025-03", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-04", "section": "§4.5, §4.6.1–4.6.3, MECIR C42", "official_principle": "Distinguish studies from reports and link them; do not omit a study solely because a result was not reported.", "review_level": "Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool" }, { "id": "M08", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-08", "section": "§8.1–8.2.3, Table 8.2.a", "official_principle": "Fix the outcome and effect of interest when reviewing randomization, deviations, missing data, measurement and selective reporting.", "review_level": "Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool" }, { "id": "M15", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2023-08", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-15", "section": "§15.2.4, §15.3.1–15.3.3", "official_principle": "Distinguish effect estimates, intervals, importance and applicability. Sample size alone does not determine precision.", "review_level": "Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool" }, { "id": "M19", "version": "Cochrane Handbook 6.5 (2024), chapter updated 2019-10", "url": "https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-19", "section": "§19.1.2, §19.2.1–19.2.4", "official_principle": "Harm questions may require different designs, populations and follow-up from efficacy questions. Case reports do not establish incidence.", "review_level": "Historical reuse of methodological principles/versions preserved in 1585 and the actual 5 HTML copies; not a new reading of full methods texts or execution of an official tool" } ], "status_dictionary": { "Partly verified": "Some content in the currently archived summaries has been verified; specific gaps in effects, preparations, denominators and original materials remain", "Unverified": "Required items could not be verified within the preserved scope; this does not mean 0 studies, no effect or safety", "Review incomplete": "Comparison with original materials/searches have not been performed within the permitted scope", "Not reported": "A status limited to the absence of the item from the specific material/section that was read", "Inaccessible": "Used only for materials for which access was actually attempted and failed. Not assigned to clinical materials in this task", "Insufficient evidence matching the conditions": "Used only when, after reviewing relevant studies within a defined scope, the evidence is insufficient to answer the condition. Not applied across the entire body of evidence in this task", "Not applicable": "For the selected acute-nausea question, separate events, optimal-dose or maintenance extensions are not imposed as additional requirements", "Conflicting records": "When materials that are difficult to reconcile have been compared for the same question, timepoint and analysis. Not assigned merely because numbers differ between reviews", "Met": "Verification of the specified question, attribution and preservation/linking; not certification of direct efficacy, pregnancy safety or full-text reading" }, "study_overlap": { "state": "The 8 source records do not mean 8 independent clinical trials. The main regimen and the supportive regimen at a different dose belong to separate trial families; the guideline and general safety, nutrition and drug information are not counted as pregnancy-nausea trials. S01: TF-SAH-1991: Main evidence, retained-summary level / S02: TF-VUT-1995: Supportive evidence, not independent same-dose replication / S03, S04, S05, S06, S07, S08: Guideline context/general safety and nutrition/drug information. Not counted as independent pregnancy-nausea trials.", "unique_trial_count": null, "unique_participant_count": null, "reason": "The 8 source records do not mean 8 independent clinical trials. The main regimen and the supportive regimen at a different dose belong to separate trial families; the guideline and general safety, nutrition and drug information are not counted as pregnancy-nausea trials. S01: TF-SAH-1991: Main evidence, archived-summary level / S02: TF-VUT-1995: Supportive evidence, not independent same-dose replication / S03, S04, S05, S06, S07, S08: Guideline context/general safety and nutrition/drug information. Not counted as independent pregnancy-nausea trials." }, "history": [ { "date": "2026-11-01", "kind": "Public view/material separation", "view_version": "1.0", "change": "The public view and materials were prepared from the existing 38 items. No new clinical search, change in verification status or scoring was performed." } ], "language": "en", "translation_date": "2026-11-01" }