Evidence dossier · candidate cand-hepatitis-b-drug-toxicity · VICP program · · DRAFT — not a determination
This is a draft research-tracking dossier, not a determination that Hepatitis B vaccine causes Drug toxicity, and not an incidence or legal finding. All evidence is flagged needs_human_review and must be reviewed before any page is published or cited. Every value is grounded in retrieved citations (PMID + retrieval date); unsourced items read "no evidence found / not assessable". Symmetric search: every supporting query has a mirror/null query, and zeros are shown (negative dossiers report the absence of signal).
Claim matrix (C1–C6, computed)
Claim
Label
Status
Missing nodes
C1
Coherent clinical object exists
insufficient_data
missing: A2
C2
Consistent temporal window
supported
C3
Epidemiologic excess risk
insufficient_data
missing: B2 B3
C4
Consistency / replication
insufficient_data
missing: B6
C5
Specificity (product / dose)
insufficient_data
missing: C1n
C6
Biological mechanism
insufficient_data
missing: E1
Two evidentiary bars apply to the epi nodes/claims (C3, C4): · VICP — preponderance of the evidence. · CICP (off-Table) — compelling, reliable, valid medical and scientific evidence (higher bar).
Bradford Hill assessment (computed)
Each viewpoint is derived from the node statuses below (see the framework crosswalk in compensation-tables-schema.md §8). Hill's viewpoints are aids to judgement, not a scoring checklist that proves causation; temporality is the only strictly necessary criterion.
Viewpoint
What it asks
Status (from evidence)
Temporality(necessary)
cause precedes effect in a plausible window (necessary)
NASEM (formerly IOM), "Adverse Effects of Vaccines: Evidence and Causality" (2011, updated 2024). Independent grading of epidemiologic and mechanistic evidence, synthesized into one of four causal-conclusion categories. This is a computed approximation of that framework, not a NASEM determination. See compensation-tables-schema.md §8bis.
Case-definition standard: no established case definition (needs_human_review — not in spec §1's named-standard list) — governs the case-certainty scale on A1/A2/A6/A8 below. See compensation-tables-schema.md §8ter.
Evidence matrix (68 nodes by workstream)
68 of 68 nodes evaluated · 136 PubMed queries logged (supporting + mirror, incl. zeros). Statuses are computed from retrieved citations; not hand-set.
Definition & attribution 24/24 evaluated
A1 · Case reportsno_data
Measure: New definite object in risk window T Comparator: Pre-vaccination baseline Hit rule: Definite object present, onset in window, competing causes considered
Finding: no evidence found
Case-certainty distribution (no established case definition): 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Case reports pubmed · 66198 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
9 retrieved record(s)
ambiguous 34935404 · AJR. American journal of roentgenology (2022) — COVID-19 Vaccine-Related Axillary Adenopathy on Breast Imaging: Follow-Up Recommendations and Histopathologic Findings.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
supports_node 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
does_not_resolve 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A2 · Series with objective confirmationno_data
Measure: Definite object plus objective test Comparator: Reference range / diagnostic criteria Hit rule: Objective confirmation in >=1 case per the working definition
Finding: no evidence found
Case-certainty distribution (no established case definition): 1 Possible/unclassifiable. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Series with objective confirmation pubmed · 5670 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
9 retrieved record(s)
does_not_resolve 34935404 · AJR. American journal of roentgenology (2022) — COVID-19 Vaccine-Related Axillary Adenopathy on Breast Imaging: Follow-Up Recommendations and Histopathologic Findings.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
ambiguous 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
does_not_resolve 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A3 · Onset histogramno_data
Measure: Distribution of onset times after dose Comparator: Pre-specified risk window Hit rule: Onset clusters inside the pre-specified window (not uniform/flat)
Finding: The retrieved evidence includes only case reports and reviews describing adverse reactions to hepatitis B vaccine such as serum sickness, lichen planus, granuloma annulare, and hypersensitivity, but no reports specifically documenting drug toxicity attributed to the hepatitis B vaccine with onset within a pre-specified risk window after competing causes assessment.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Onset histogram pubmed · 29 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
supports_node 12403239 · Journal of the Medical Association of Th (2002) — Serum sickness and hepatitis B vaccine including review of the literature.
supports_node 15324406 · Journal of the European Academy of Derma (2004) — Two case reports of cutaneous adverse reactions following hepatitis B vaccine: lichen planus and granuloma annulare.
ambiguous 32402623 · Allergologia et immunopathologia (2020) — Adverse reaction with hexavalent vaccine: An unusual case.
ambiguous 1679511 · Lancet (London, England) (1991) — Hypersensitivity to thiomersal in hepatitis B vaccine.
supports_node 41766243 · Indian journal of pharmacology (2026) — Adverse drug reaction due to concomitant vaccine administration of Covishield and Hepatitis-B in a patient with multidrug allergies.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
supports_node 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
A4 · Temporal plausibilityno_data
Measure: Onset latency vs object pathophysiology Comparator: Object's known natural latency Hit rule: Onset latency consistent with the object's pathophysiology
Finding: No retrieved evidence addresses temporal plausibility for drug toxicity attributed to the Hepatitis B vaccine with onset latency consistent with the object's pathophysiology; the only Hepatitis B vaccine-related study (PMID 15638050) describes autoimmune and other conditions but does not specify onset latency relative to vaccine pathophysiology.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Temporal plausibility pubmed · 58 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
10 retrieved record(s)
supports_node 15638050 · Clinical and experimental rheumatology (2004) — A case-series of adverse events, positive re-challenge of symptoms, and events in identical twins following hepatitis B vaccination: analysis of the Vaccine Adv
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
supports_node 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
ambiguous 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
supports_node 40046048 · Frontiers in immunology (2025) — The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis.
A5 · Onset-interval documentationno_data
Measure: Onset interval documented in source Comparator: Dose date Hit rule: Onset interval is recorded (not imputed) in a primary source
Finding: No retrieved evidence documents the onset interval for drug toxicity attributed to hepatitis B vaccine; the few case reports mentioning onset timing (e.g., PMID 15324406 reports onset of lichen planus at 3 weeks post-dose) do not address onset-interval documentation in a primary source as defined for this node.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Onset-interval documentation pubmed · 27 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
supports_node 12403239 · Journal of the Medical Association of Th (2002) — Serum sickness and hepatitis B vaccine including review of the literature.
supports_node 15324406 · Journal of the European Academy of Derma (2004) — Two case reports of cutaneous adverse reactions following hepatitis B vaccine: lichen planus and granuloma annulare.
ambiguous 32402623 · Allergologia et immunopathologia (2020) — Adverse reaction with hexavalent vaccine: An unusual case.
ambiguous 1679511 · Lancet (London, England) (1991) — Hypersensitivity to thiomersal in hepatitis B vaccine.
supports_node 41766243 · Indian journal of pharmacology (2026) — Adverse drug reaction due to concomitant vaccine administration of Covishield and Hepatitis-B in a patient with multidrug allergies.
does_not_resolve 34935404 · AJR. American journal of roentgenology (2022) — COVID-19 Vaccine-Related Axillary Adenopathy on Breast Imaging: Follow-Up Recommendations and Histopathologic Findings.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
A6 · Differential diagnosis excludedno_data
Measure: Competing causes assessed and excluded Comparator: Likely alternative diagnoses Hit rule: Pre-specified competing causes ruled out per the working definition
Finding: no evidence found
Case-certainty distribution (no established case definition): 1 Definite. Transparency layer — does not change this node's status or feed C1–C6.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Differential diagnosis excluded pubmed · 454 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
9 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
ambiguous 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
ambiguous 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
supports_node 40046048 · Frontiers in immunology (2025) — The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A7 · Rechallenge / re-exposureno_data
Measure: Object recurs on a further dose Comparator: First-dose response Hit rule: Object recurs after a subsequent dose (re-exposure)
Finding: No retrieved evidence specifically documents recurrence of drug toxicity attributed to Hepatitis B vaccine after rechallenge (a subsequent dose).
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Rechallenge / re-exposure pubmed · 29 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
supports_node 12403239 · Journal of the Medical Association of Th (2002) — Serum sickness and hepatitis B vaccine including review of the literature.
supports_node 15324406 · Journal of the European Academy of Derma (2004) — Two case reports of cutaneous adverse reactions following hepatitis B vaccine: lichen planus and granuloma annulare.
ambiguous 32402623 · Allergologia et immunopathologia (2020) — Adverse reaction with hexavalent vaccine: An unusual case.
ambiguous 1679511 · Lancet (London, England) (1991) — Hypersensitivity to thiomersal in hepatitis B vaccine.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
does_not_resolve 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
A8 · Adjudicated by criteria (no established case definition)no_data
Measure: Object adjudicated by published criteria Comparator: Published clinical / Brighton criteria Hit rule: Cases adjudicated to 'definite' by a published criterion set
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Adjudicated by criteria pubmed · 66 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
9 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
ambiguous 30000765 · (2006) — Human Papillomavirus Vaccines.
supports_node 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
ambiguous 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
supports_node 40046048 · Frontiers in immunology (2025) — The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis.
ambiguous 7114977 · Archives of internal medicine (1982) — Vaccine-related poliomyelitis.
A9 · Natural-history consistencyno_data
Measure: Course matches the object's natural history Comparator: Known natural history of the object Hit rule: Clinical course (onset, peak, recovery) matches the object's natural history
Finding: No retrieved evidence addresses Hepatitis B vaccine and drug toxicity; all evidence pertains to SARS-CoV-2, HPV, or other vaccines, with no mention of Hepatitis B vaccine or drug toxicity natural-history consistency.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series Natural-history consistency pubmed · 130 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
9 retrieved record(s)
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
supports_node 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
supports_node 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
ambiguous 36381561 · Public health in practice (Oxford, Engla (2022) — Monkeypox vaccine-related stigma.
ambiguous 40046048 · Frontiers in immunology (2025) — The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis.
does_not_resolve 36441403 · Current cardiology reports (2022) — COVID-19 Vaccine-Related Myocardial and Pericardial Inflammation.
A10 · No confounding objectno_data
Measure: Not attributable to a co-occurring condition Comparator: Co-occurring illness that could produce the object Hit rule: Object not better explained by a co-occurring condition (infection, etc.)
Finding: No retrieved evidence directly addresses new drug toxicity attributed to Hepatitis B vaccine; the only possibly relevant PMID (23611823) has no abstract and cannot be assessed, and all other retrieved evidence concerns other vaccines or drugs.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity case report OR case series No confounding object pubmed · 46 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity alternative diagnosis OR not vaccine-related pubmed · 4053 hits · run 2026-09-07
does_not_resolve 34312836 · Clinical pharmacology and therapeutics (2022) — Angiotensin-Converting Enzyme Inhibitors Used Concomitantly with Insulin Secretagogues and the Risk of Serious Hypoglycemia.
does_not_resolve 34935404 · AJR. American journal of roentgenology (2022) — COVID-19 Vaccine-Related Axillary Adenopathy on Breast Imaging: Follow-Up Recommendations and Histopathologic Findings.
ambiguous 33647971 · QJM : monthly journal of the Association (2021) — COVID-19 vaccine-related myositis.
ambiguous 37775180 · Clinical medicine (London, England) (2023) — SARS-CoV-2 vaccines and myocarditis.
does_not_resolve 30000765 · (2006) — Human Papillomavirus Vaccines.
supports_node 36560483 · Vaccines (2022) — Vaccine-Related Autoimmune Hepatitis: Emerging Association with SARS-CoV-2 Vaccination or Coincidence?
D1 · Predicted site of injuryno_data
Measure: Object at the site the mechanism predicts Comparator: Predicted anatomic site from the mechanism Hit rule: Object localizes to the anatomic site the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity anatomic localization Predicted site of injury mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Predicted site of injury not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D2 · Spared structuresno_data
Measure: Structures the mechanism should spare are spared Comparator: Structures predicted unaffected Hit rule: Structures predicted spared by the mechanism are indeed spared
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity anatomic localization Spared structures mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Spared structures not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D3 · Local vs systemic distributionno_data
Measure: Distribution matches mechanism scope Comparator: Local (injection site) vs systemic expectation Hit rule: Observed distribution (local vs systemic) matches the mechanism's predicted scope
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity anatomic localization Local vs systemic distribution mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Local vs systemic distribution not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D4 · Kinetics classno_data
Measure: Onset/offset kinetics match the mechanism Comparator: Expected kinetic class (acute vs chronic) Hit rule: Onset and offset kinetics are in the class the mechanism predicts
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity anatomic localization Kinetics class mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Kinetics class not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
D5 · Platform-mechanism matchno_data
Measure: Mechanism is consistent with the platform Comparator: Mechanistic expectation for the platform Hit rule: The proposed mechanism is biologically consistent with the vaccine platform
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity anatomic localization Platform-mechanism match mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Platform-mechanism match not consistent with mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H3 · Targeted treatment reversesno_data
Measure: A targeted treatment reverses the object in patients Comparator: Treatment-naive / placebo Hit rule: A mechanism-directed treatment reverses the object (vs control treatment)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Targeted treatment reverses intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Targeted treatment reverses no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I1 · No internal contradictionno_data
Measure: No node's finding contradicts another Comparator: Internal consistency across nodes Hit rule: No evaluated node directly contradicts another (coherence)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity No internal contradiction coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity No internal contradiction inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
2 retrieved record(s)
ambiguous 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
does_not_resolve 19477561 · Vaccine (2009) — Genetic polymorphisms in host response to meningococcal infection: the role of susceptibility and severity genes.
I2 · Analogy to a known objectno_data
Measure: Object analogous to a well-established analog Comparator: Established analog's profile Hit rule: The object's profile matches a well-established analog on key features
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Analogy to a known object coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Analogy to a known object inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
I5 · Latency coherenceno_data
Measure: Observed latency matches the mechanism's latency Comparator: Mechanism-predicted latency Hit rule: Observed onset latency is coherent with the mechanism's predicted latency
Finding: The retrieved evidence discusses melanoma risk factors and ultraviolet radiation but does not address latency coherence for Hepatitis B vaccine-attributed drug toxicity.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Latency coherence coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Latency coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 2699706 · Annali italiani di chirurgia (1989) — Etiology and risk factors of melanoma.
J1 · Pre-specificationno_data
Measure: Window/hit-rule pre-specified before data Comparator: Pre-specified vs post-hoc Hit rule: The risk window, object, and hit rule were pre-specified before data were seen
Finding: The retrieved evidence discusses the use of large language models to identify immune-related adverse events and drug-induced acute kidney injury risk prediction, but does not address pre-specification of risk windows or hit rules for Hepatitis B vaccine and drug toxicity.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Pre-specification pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Pre-specification post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Measure: Contrary evidence is logged, not omitted Comparator: Support-only dossier Hit rule: Contrary / null / refuting findings are logged and shown alongside support
Finding: No evidence found.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Contrary-evidence log pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Contrary-evidence log post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J3 · No temporality-only claimno_data
Measure: Claim not based on temporality alone Comparator: Sequence-only evidence Hit rule: The claim is not supported by temporal sequence alone (independent evidence exists)
Finding: The retrieved evidence discusses immune-related adverse events from immune checkpoint inhibitors and drug-induced acute kidney injury risk prediction, but does not mention Hepatitis B vaccine or drug toxicity attributed to that vaccine.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity No temporality-only claim pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity No temporality-only claim post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Measure: Passive-surveillance findings bounded correctly Comparator: Active-surveillance confirmation Hit rule: Passive-surveillance signals are framed as hypothesis-generating, not confirmatory
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Passive-surveillance role pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Passive-surveillance role post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
ambiguous 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
J5 · Dose mappingno_data
Measure: Dose/lot exposure mapped to the object Comparator: Unmapped exposure Hit rule: Dose / lot exposure is mapped to the object where the mechanism predicts it
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Dose mapping pre-specified OR adjudicated pubmed · 13550 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Dose mapping post-hoc OR hypothesis-generating only pubmed · 1700 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 39226489 · Journal of clinical oncology : official (2024) — Enhancing Precision in Detecting Severe Immune-Related Adverse Events: Comparative Analysis of Large Language Models and International Classification of Disease
Epidemiologic chassis 13/13 evaluated
B1 · Excess vs baselineno_data
Measure: RR/IRR vs unexposed or prior window Comparator: Unvaccinated person-time or pre-vaccination window Hit rule: RR/IRR > 1 with CI excluding 1 after pre-specified confounders
Finding: No evidence retrieved addresses the association between Hepatitis B vaccine and drug toxicity; all retrieved studies focus on antipsychotics, herpes zoster vaccine, tirzepatide, or NAFLD.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Excess vs baseline incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Excess vs baseline pubmed · 88507 hits · run 2026-09-07
6 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
refutes_node 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 34672967 · Lancet (London, England) (2021) — Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, pha
does_not_resolve 34489307 · Gut (2022) — Non-alcoholic fatty liver disease and incident major adverse cardiovascular events: results from a nationwide histology cohort.
B2 · SCCSno_data
Measure: Self-controlled case series risk ratio Comparator: Individuals' own risk intervals (no-event) Hit rule: SCCS risk ratio > 1 in the post-vaccination window, CI excluding 1
Finding: No retrieved evidence directly addresses the risk of drug toxicity attributed to Hepatitis B vaccine using a self-controlled case series (SCCS) design with a risk ratio >1 and confidence interval excluding 1.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity SCCS incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk SCCS pubmed · 88614 hits · run 2026-09-07
5 retrieved record(s)
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 39795956 · International journal of molecular scien (2024) — The Potential Metalloestrogenic Effect of Aluminum on Breast Cancer Risk for Antiperspirant Users.
does_not_resolve 30941541 · Cancer causes & control : CCC (2019) — Diabetes, obesity, and subsequent risk of postmenopausal breast cancer among white and black women in the Southern Community Cohort Study.
B3 · Cohort / risk-intervalno_data
Measure: Incidence rate ratio in defined window Comparator: Pre-specified risk vs comparison interval Hit rule: IRR > 1 in the pre-specified window, CI excluding 1, stratified by age/sex
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Cohort / risk-interval incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Cohort / risk-interval pubmed · 88116 hits · run 2026-09-07
4 retrieved record(s)
ambiguous 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
ambiguous 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 37082039 · Journal of oral and maxillofacial pathol (2022) — Null genotypes of Glutathione S-transferase M1 and T1 and risk of oral cancer: A meta-analysis.
does_not_resolve 23296061 · Gene (2013) — Null genotypes of GSTM1 and GSTT1 contribute to increased risk of diabetes mellitus: a meta-analysis.
B4 · Meta-analysis / poolingno_data
Measure: Pooled effect across studies Comparator: Pooled estimate with heterogeneity Hit rule: Pooled estimate > 1 (or < 1) with quantified heterogeneity (I2)
Finding: No evidence found. The retrieved evidence addresses antipsychotic-associated cardiovascular risk, SCCS methodology in vaccine safety, herpes zoster vaccine safety, and fall-risk-increasing drugs, with no mention of hepatitis B vaccine or drug toxicity attributed to it.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Meta-analysis / pooling incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Meta-analysis / pooling pubmed · 111953 hits · run 2026-09-07
4 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 29402646 · Journal of the American Medical Director (2018) — Fall-Risk-Increasing Drugs: A Systematic Review and Meta-analysis: III. Others.
B5 · Negative-control outcomesno_data
Measure: No excess for outcomes the vaccine should not cause Comparator: Negative-control outcomes (unaffected by mechanism) Hit rule: Null for negative-control outcomes while target outcome is positive (specificity)
Finding: The retrieved evidence includes studies on COVID-19 XBB.1.5 vaccination, Shingrix vaccination, rotavirus vaccination, and valproate use during spermatogenesis; none address drug toxicity as a negative-control outcome following Hepatitis B vaccination.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Negative-control outcomes incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Negative-control outcomes pubmed · 88318 hits · run 2026-09-07
6 retrieved record(s)
refutes_node 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 38875047 · The International journal of risk & safe (2024) — Self-controlled risk interval study of rotavirus vaccine safety: Findings and implications.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 38833248 · JAMA network open (2024) — Valproate Use During Spermatogenesis and Risk to Offspring.
B6 · Other-antigen comparisonno_data
Measure: Risk vs a different-antigen comparator Comparator: Comparator product with a different antigen Hit rule: Risk specific to the target antigen, not shared with the comparator antigen
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Other-antigen comparison incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Other-antigen comparison pubmed · 88080 hits · run 2026-09-07
6 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
does_not_resolve 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
ambiguous 23238161 · European journal of dermatology : EJD (2013) — Hypersensitivity and vaccines: an update.
does_not_resolve 27996332 · Expert review of vaccines (2017) — DTaP5-IPV-Hib-HepB, a hexavalent vaccine for infants and toddlers.
does_not_resolve 23296494 · Molecular biology reports (2013) — Assessment of the association between GSTM1 null genotype and risk of type 2 diabetes.
B7 · Absolute riskno_data
Measure: Per-100k risk in window Comparator: Absolute incidence per 100k Hit rule: Absolute risk reported and stable across the window (not an artifact of rarity)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Absolute risk incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Absolute risk pubmed · 111353 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
refutes_node 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
refutes_node 40716143 · Vaccine (2025) — Tinnitus risk after COVID-19 XBB.1.5 vaccination: A self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 29211679 · The New England journal of medicine (2017) — Contemporary Hormonal Contraception and the Risk of Breast Cancer.
does_not_resolve 23484825 · The New England journal of medicine (2013) — Risk of ischemic heart disease in women after radiotherapy for breast cancer.
does_not_resolve 26950145 · Nutrients (2016) — An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.
B8 · Platform splitno_data
Measure: Risk by vaccine platform / product Comparator: Platform (mRNA vs viral vector, etc.) Hit rule: Risk attributable to a specific platform, not to 'a vaccine' generally
Finding: The retrieved evidence does not address drug toxicity from hepatitis B vaccine by vaccine platform; it focuses on antipsychotic-associated events and herpes zoster vaccine safety using self-controlled case series designs.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Platform split incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Platform split pubmed · 88145 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
refutes_node 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
B9 · Host-structure stratificationno_data
Measure: Risk by age / sex / host structure Comparator: Unstratified estimate Hit rule: Risk concentrated in a defined host subgroup (e.g. young males), stable across sources
Finding: No retrieved evidence addresses hepatitis B vaccine or drug toxicity; all four PMIDs focus on antipsychotics or shingles vaccines.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Host-structure stratification incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Host-structure stratification pubmed · 88078 hits · run 2026-09-07
4 retrieved record(s)
does_not_resolve 34751642 · Epidemiology and psychiatric sciences (2021) — Cardiovascular and metabolic risk of antipsychotics in children and young adults: a multinational self-controlled case series study.
does_not_resolve 37468475 · Nature communications (2023) — Herpes zoster vaccine safety in the Aotearoa New Zealand population: a self-controlled case series study.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
B10 · Formulation / component changeno_data
Measure: Risk tracks a formulation change Comparator: Pre- vs post-change formulation Hit rule: Risk change tracks a documented formulation / component change over time
Finding: The retrieved evidence discusses self-controlled case series (SCCS) methodology and its application to vaccine safety studies, but none of the abstracts mention a formulation or component change for Hepatitis B vaccine, nor do they assess Drug toxicity risk tracking a specific formulation change over time.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Formulation / component change incidence risk cohort OR self-controlled case series pubmed · 945 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no association OR null OR no increased risk Formulation / component change pubmed · 88240 hits · run 2026-09-07
3 retrieved record(s)
does_not_resolve 34937500 · Expert review of vaccines (2022) — Self-controlled case series design in vaccine safety: a systematic review.
does_not_resolve 30851046 · Biostatistics (Oxford, England) (2020) — ConvSCCS: convolutional self-controlled case series model for lagged adverse event detection.
does_not_resolve 40664645 · Nature communications (2025) — Evaluating the safety of XBB.1.5-containing COVID-19 mRNA vaccines using a self-controlled case series study.
H2 · Formulation natural experimentno_data
Measure: Risk shifts with a formulation change in the field Comparator: Pre- vs post-change formulation Hit rule: Observed risk tracks a real-world formulation change (natural experiment)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Formulation natural experiment intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Formulation natural experiment no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H4 · Policy / pause signalno_data
Measure: Risk signal appears/disappears across a pause or policy change Comparator: Pre- vs post-pause period Hit rule: The signal appears or disappears coherently with a rollout / pause (H4)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Policy / pause signal intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Policy / pause signal no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
1 retrieved record(s)
does_not_resolve 38189107 · Expert review of vaccines (2024) — Neoadjuvant personalized cancer vaccines: the final frontier?
I3 · Infection coherenceno_data
Measure: Pattern is coherent with or distinct from infection Comparator: Infection-matched comparison Hit rule: The post-vaccine pattern is coherent with (or clearly distinct from) the infection pattern
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Infection coherence coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Infection coherence inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 15578364 · Clinical infectious diseases : an offici (2004) — Varicella vaccine for susceptible adults: do it today.
Mediator & biological gradient 24/24 evaluated
C1n · Dose strength gradientno_data
Measure: Risk vs dose strength (dose size) Comparator: Lower dose strength Hit rule: Monotonic dose-response in dose strength (larger dose -> higher risk)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Dose strength gradient dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no dose effect OR no dose-response Dose strength gradient pubmed · 159 hits · run 2026-09-07
4 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 34505706 · Journal of the American Geriatrics Socie (2021) — Association between vitamin D status and long-term falls-related hospitalization risk in older women.
ambiguous 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
ambiguous 39396824 · Human vaccines & immunotherapeutics (2024) — Adverse event reporting following immunization of hepatitis B vaccine: A 13-year review.
C2n · Dose number gradientno_data
Measure: Risk vs dose number (1st vs 2nd vs 3rd) Comparator: First dose Hit rule: Risk increases (or shows a defined pattern) with dose number
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Dose number gradient dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no dose effect OR no dose-response Dose number gradient pubmed · 603 hits · run 2026-09-07
4 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
refutes_node 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
does_not_resolve 39396824 · Human vaccines & immunotherapeutics (2024) — Adverse event reporting following immunization of hepatitis B vaccine: A 13-year review.
does_not_resolve 42488947 · Hypertension (Dallas, Tex. : 1979) (2026) — Clinical Modifiers of Salt Sensitivity: A Meta-Regression and Risk Translation Study.
C3n · Measured-exposure tertilesno_data
Measure: Risk vs measured exposure tertile Comparator: Lowest-exposure tertile Hit rule: Risk ordered by measured-exposure tertile (high > mid > low)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Measured-exposure tertiles dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no dose effect OR no dose-response Measured-exposure tertiles pubmed · 48 hits · run 2026-09-07
11 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 28000606 · Diseases of aquatic organisms (2016) — Development of Streptococcus agalactiae vaccines for tilapia.
refutes_node 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
does_not_resolve 39396824 · Human vaccines & immunotherapeutics (2024) — Adverse event reporting following immunization of hepatitis B vaccine: A 13-year review.
ambiguous 26208678 · Human vaccines & immunotherapeutics (2015) — Hepatitis B and A vaccination in HIV-infected adults: A review.
does_not_resolve 16370953 · Expert opinion on drug safety (2006) — When science is not enough - a risk/benefit profile of thiomersal-containing vaccines.
does_not_resolve 28573913 · Expert review of vaccines (2017) — The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.
refutes_node 17576737 · Lupus (2007) — Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus.
C4n · Organoid concentration curveno_data
Measure: Effect vs antigen concentration in organoid Comparator: Vehicle / zero antigen Hit rule: Dose-dependent effect across a graded concentration curve
Finding: No retrieved evidence addresses dose-dependent effects of Hepatitis B vaccine across a graded concentration curve in organoids; only clinical safety data, systematic reviews of immunogenicity, and thiomersal-related hypersensitivity reports were retrieved.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Organoid concentration curve dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no dose effect OR no dose-response Organoid concentration curve pubmed · 59 hits · run 2026-09-07
8 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
refutes_node 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
does_not_resolve 39396824 · Human vaccines & immunotherapeutics (2024) — Adverse event reporting following immunization of hepatitis B vaccine: A 13-year review.
ambiguous 26208678 · Human vaccines & immunotherapeutics (2015) — Hepatitis B and A vaccination in HIV-infected adults: A review.
refutes_node 16370953 · Expert opinion on drug safety (2006) — When science is not enough - a risk/benefit profile of thiomersal-containing vaccines.
does_not_resolve 28573913 · Expert review of vaccines (2017) — The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.
refutes_node 17576737 · Lupus (2007) — Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus.
does_not_resolve 27629913 · Human vaccines & immunotherapeutics (2017) — Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.
C5n · EC50 vs Cmax coherenceno_data
Measure: Measured exposure reaches effect threshold Comparator: Pharmacokinetic Cmax vs EC50 Hit rule: Achieved exposure (Cmax/tissue) plausibly reaches the in-vitro EC50
Finding: No retrieved evidence provides pharmacokinetic or exposure data (e.g., Cmax, tissue concentration, EC50) relevant to whether achieved exposure from hepatitis B vaccine plausibly reaches an in-vitro EC50 for drug toxicity.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity EC50 vs Cmax coherence dose-response OR dose effect pubmed · 1299193 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity no dose effect OR no dose-response EC50 vs Cmax coherence pubmed · 48 hits · run 2026-09-07
10 retrieved record(s)
does_not_resolve 39082700 · The Journal of infectious diseases (2025) — Effectiveness of MenB-4C Vaccine Against Gonorrhea: A Systematic Review and Meta-analysis.
does_not_resolve 15146581 · Bulletin de l'Academie nationale de mede (2003) — [Mercury in vaccines].
does_not_resolve 39396824 · Human vaccines & immunotherapeutics (2024) — Adverse event reporting following immunization of hepatitis B vaccine: A 13-year review.
ambiguous 26208678 · Human vaccines & immunotherapeutics (2015) — Hepatitis B and A vaccination in HIV-infected adults: A review.
refutes_node 17576737 · Lupus (2007) — Safety and efficacy of hepatitis B vaccine in systemic lupus erythematosus.
does_not_resolve 16370953 · Expert opinion on drug safety (2006) — When science is not enough - a risk/benefit profile of thiomersal-containing vaccines.
does_not_resolve 28573913 · Expert review of vaccines (2017) — The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.
does_not_resolve 27629913 · Human vaccines & immunotherapeutics (2017) — Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.
E1 · Mediator identified in casesno_data
Measure: Mediator present in affected tissue/cells Comparator: Unaffected tissue / control Hit rule: The hypothesized mediator is detected in the affected compartment and not (or less) in control
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Mediator identified in cases in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Mediator identified in cases not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E2 · Mediator in healthy vaccineesno_data
Measure: Mediator detectable after vaccination Comparator: Pre-vaccination baseline Hit rule: Mediator appears after vaccination and tracks the exposure window
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Mediator in healthy vaccinees in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Mediator in healthy vaccinees not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E3 · Infection contrastno_data
Measure: Mediator absent/low after natural infection Comparator: Recovered natural infection Hit rule: Mediator signal is specific to vaccination vs a comparable natural-infection control
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Infection contrast in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Infection contrast not associated mechanism pubmed · 2 hits · run 2026-09-07
1 retrieved record(s)
does_not_resolve 26144895 · Vaccine (2015) — Efficacy of antigen dosage on the hepatitis B vaccine response in infants born to hepatitis B-uninfected and hepatitis B-infected mothers.
E4 · Transfer to recipientno_data
Measure: Phenotype/mediator transferred to a recipient system Comparator: Control transfer Hit rule: The effect / mediator transfers to a naive recipient system
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Transfer to recipient in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Transfer to recipient not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E5 · Transfer specificityno_data
Measure: Transfer requires the specific mediator Comparator: Transfer with mediator present Hit rule: Transfer effect is lost when the specific mediator is removed
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Transfer specificity in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Transfer specificity not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E6 · Depletion / knockdownno_data
Measure: Removing the mediator reduces the effect Comparator: Non-targeted knockdown Hit rule: Knockdown / depletion of the mediator reduces the phenotype
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Depletion / knockdown in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Depletion / knockdown not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E7 · Add-back rescueno_data
Measure: Adding the mediator restores the effect Comparator: Add-back of a control protein Hit rule: Adding back the mediator (not a control) restores the phenotype
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Add-back rescue in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Add-back rescue not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
E8 · Neutralizationno_data
Measure: Neutralizing the mediator blocks the effect Comparator: Isotype control Hit rule: Neutralization of the mediator (not an isotype control) blocks the phenotype
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Neutralization in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Neutralization not associated mechanism pubmed · 2 hits · run 2026-09-07
2 retrieved record(s)
does_not_resolve 26100924 · Vaccine (2015) — Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.
does_not_resolve 1984386 · Annals of internal medicine (1991) — The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials
E9 · Isotype controlno_data
Measure: Isotype control does not reproduce the effect Comparator: Active antibody Hit rule: An isotype control fails to reproduce the block/activation
Finding: No evidence retrieved addresses isotype control failure to reproduce a block/activation in the context of hepatitis B vaccine-associated drug toxicity.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Isotype control in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Isotype control not associated mechanism pubmed · 7 hits · run 2026-09-07
7 retrieved record(s)
does_not_resolve 30961686 · Die Pharmazie (2019) — Adjuvant effect of Vernonia amygdalina leaf extract on host immune response to hepatitis B virus subunit vaccine.
does_not_resolve 29223483 · Vaccine (2018) — Differences by sex in IgG levels following infant and childhood vaccinations: An individual participant data meta-analysis of vaccination studies.
does_not_resolve 28464026 · PLoS neglected tropical diseases (2017) — Safety and immunogenicity of the Na-GST-1 hookworm vaccine in Brazilian and American adults.
does_not_resolve 26100924 · Vaccine (2015) — Immunogenicity and safety of an E. coli-produced bivalent human papillomavirus (type 16 and 18) vaccine: A randomized controlled phase 2 clinical trial.
does_not_resolve 23432812 · BMC infectious diseases (2013) — Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese i
does_not_resolve 15367337 · Xi bao yu fen zi mian yi xue za zhi = Ch (2004) — [Immunogenicity of a multiple epitope DNA vaccine against hepatitis B virus].
does_not_resolve 19635606 · Vaccine (2009) — Recombinant interferon-alpha2b improves immune response to hepatitis B vaccination in haemodialysis patients: results of a randomised clinical trial.
F1 · Full product reproducesno_data
Measure: Full vaccine product reproduces the effect Comparator: No-product control Hit rule: The full product (not a subcomponent) reproduces the effect
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Full product reproduces component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Full product reproduces no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
F2 · Empty vector / particleno_data
Measure: Vector/particle without antigen reproduces (or not) Comparator: Full product Hit rule: Effect attributed to (or excluded from) the vector/particle backbone alone
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Empty vector / particle component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Empty vector / particle no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
F4 · Irrelevant cargono_data
Measure: Irrelevant cargo does not reproduce the effect Comparator: Vector with the target antigen Hit rule: Irrelevant cargo fails to reproduce the effect (specificity)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Irrelevant cargo component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Irrelevant cargo no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
F5 · Infection preparationno_data
Measure: Infection preparation vs product comparison Comparator: Product-derived preparation Hit rule: Effect compares correctly between infection and product preparations
Finding: No retrieved evidence addresses drug toxicity attributed to Hepatitis B vaccine, infection preparation versus product comparison, or adverse events in humans.
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Infection preparation component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Infection preparation no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
5 retrieved record(s)
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 25876176 · Human vaccines & immunotherapeutics (2015) — Progress on adenovirus-vectored universal influenza vaccines.
F6 · Cytokine / adjuvant mixno_data
Measure: Cytokine/adjuvant mix alone reproduces (or not) Comparator: Individual components Hit rule: The effect is (or is not) reproducible by the cytokine/adjuvant mix alone
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Cytokine / adjuvant mix component OR antigen OR vector pubmed · 2045311 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Cytokine / adjuvant mix no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 31300111 · Comparative immunology, microbiology and (2019) — Construction of recombinant capripoxviruses as vaccine vectors for delivering foreign antigens: Methodology and application.
does_not_resolve 42172979 · Virology (2026) — Towards the development of a mucosal vectored vaccine against enterovirus D68.
does_not_resolve 21952287 · Cancer journal (Sudbury, Mass.) (2011) — Viral vector-based therapeutic cancer vaccines.
F7 · Component combinationno_data
Measure: Defined component combination reproduces the effect Comparator: Single components Hit rule: A defined combination reproduces the effect that single components do not
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Component combination component OR antigen OR vector pubmed · 2045314 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Component combination no effect component isolation pubmed · 0 hits (0 hits — negative) · run 2026-09-07
does_not_resolve 34816398 · Methods in molecular biology (Clifton, N (2022) — Avian Paramyxoviruses as Vectors for Vaccine Development.
does_not_resolve 15174971 · Expert opinion on biological therapy (2004) — Particle-mediated DNA vaccine delivery to the skin.
does_not_resolve 29550258 · Immunology letters (2018) — Live bacterial vaccine vector and delivery strategies of heterologous antigen: A review.
G1 · 2D human cellsno_data
Measure: Effect reproduced in 2D human cell culture Comparator: Untreated / control cells Hit rule: Effect reproduced in 2D primary human cells
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity 2D human cells animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity 2D human cells not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G2 · Organoid / chipno_data
Measure: Effect reproduced in organoid / organ-on-chip Comparator: Unexposed organoid Hit rule: Effect reproduced in a 3D organoid / organ-on-chip system
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Organoid / chip animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Organoid / chip not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
H1 · Block in vitro / in vivono_data
Measure: Blocking the mediator/mechanism prevents the effect Comparator: Control intervention Hit rule: Blocking the mechanism prevents or reverses the effect (not with a control intervention)
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Block in vitro / in vivo intervention OR treatment OR reversal pubmed · 15142392 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Block in vitro / in vivo no effect intervention pubmed · 0 hits (0 hits — negative) · run 2026-09-07
Clinical / animal / host 7/7 evaluated
E10 · Host-line dependenceno_data
Measure: Effect depends on host line/cell type Comparator: Susceptible host line Hit rule: Effect is restricted to a defined host line / genotype, not universal
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity mechanism Host-line dependence in vitro OR patient-derived pubmed · 29244 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Host-line dependence not associated mechanism pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G3 · Animal, clinical routeno_data
Measure: Effect in animal via the clinical route of administration Comparator: Vehicle, same route Hit rule: Effect reproduced in an animal using the clinical route of administration
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Animal, clinical route animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Animal, clinical route not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G4 · Susceptible animalno_data
Measure: Effect in a susceptible animal model Comparator: Non-susceptible model Hit rule: Effect in a defined susceptible animal model
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Susceptible animal animal OR organoid OR cell model pubmed · 1818664 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Susceptible animal not reproduced model pubmed · 1 hits · run 2026-09-07
G5 · Replication across labsno_data
Measure: Effect replicated in an independent lab Comparator: Original result Hit rule: The key effect is replicated in an independent laboratory
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Replication across labs animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Replication across labs not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G6 · Blinded scoringno_data
Measure: Outcomes scored blinded Comparator: Unblinded reference Hit rule: Primary outcomes scored by a blinded assessor
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Blinded scoring animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Blinded scoring not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
G7 · Experimental time courseno_data
Measure: Effect follows a defined experimental time course Comparator: No-exposure time course Hit rule: The effect's onset/offset follows a defined experimental time course
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Experimental time course animal OR organoid OR cell model pubmed · 1818663 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Experimental time course not reproduced model pubmed · 0 hits (0 hits — negative) · run 2026-09-07
I4 · Susceptibility traitno_data
Measure: A host trait / marker defines susceptibility Comparator: Trait-negative hosts Hit rule: A defined host trait / marker enriches for susceptibility
Finding: no evidence found
Cited: (none)
supporting: Hepatitis B vaccine Drug toxicity Susceptibility trait coherence OR latency OR susceptibility pubmed · 870068 hits · run 2026-09-07
mirror: Hepatitis B vaccine Drug toxicity Susceptibility trait inconsistent OR contradicts pubmed · 27612 hits · run 2026-09-07
How this was built
Per node: a supporting and a mirror PubMed query built from the node's measure / population / comparator / hit_rule; top hits fetched (title + abstract); each record classified (supports / refutes / ambiguous) by xAI with a heuristic fallback; a per-node synthesis is generated strictly from the retrieved PMIDs; the node status is then rolled up to C1–C6. Full query provenance is shown per node above. Reproduce the build: python -m evidence_run. Data: data/evidence_run/state.json.