{ "title": "Vitamin B6: pyridoxine monotherapy × Reduced nausea severity in early pregnancy", "criteria_version": "NGM-v3096-ORAL-PYRIDOXINE-EARLY-PREGNANCY-NAUSEA-1.1", "criteria_date": "2026-10-05", "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" }, "schema_version": "chamgap-public-criteria-1.0", "condition_origin": "Chamgap’s own application conditions", "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." }, { "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." } ], "language": "en", "translation_date": "2026-11-01" }