@pikaa-ai/pikaa 0.3.1 → 0.3.4

package/skills/hypothesis-generation/assets/source_ledger.csv

@@ -1,37 +0,0 @@
-source_id,organization,title,version_or_date,source_type,url,verified_on,status,notes
-SRC-NIH-RIGOR,National Institutes of Health,Guidance: Rigor and Reproducibility in Grant Applications,Page updated 2024-10-16,official guidance,https://grants.nih.gov/policy-and-compliance/policy-topics/reproducibility/guidance,2026-07-23,current_official,"Scientific premise, rigorous design, biological variables, resource authentication, and transparency"
-SRC-NIH-REPLICATION,National Institutes of Health,Strengthening Replication and Reproducibility of NIH-funded Research,Page reviewed 2026-06-22,official initiative,https://www.nih.gov/replicationandreproducibility,2026-07-23,current_official,"Agency-wide replication and reproducibility initiative; policy implementation may continue to evolve"
-SRC-COCHRANE-PICO,Cochrane,Handbook Chapter 2: Determining the scope of the review and the questions it will address,Current handbook chapter,official handbook,https://www.cochrane.org/authors/handbooks-and-manuals/handbook/current/chapter-02,2026-07-23,current_official,"PICO for intervention reviews, protocol-stage definition, synthesis-level distinctions, and stakeholder input"
-SRC-PICO-ORIGINAL,Richardson et al.,The well-built clinical question: a key to evidence-based decisions,Published 1995-11-01,primary methods article,https://www.acpjournals.org/doi/10.7326/ACPJC-1995-123-3-A12,2026-07-23,foundational_primary,"Original four-part well-built clinical-question article; DOI 10.7326/ACPJC-1995-123-3-A12"
-SRC-FINER-1988,Hulley and Cummings,Designing Clinical Research: An Epidemiologic Approach,First edition 1988,foundational book metadata,https://books.google.com/books/about/Designing_Clinical_Research.html?id=hKdpAAAAMAAJ,2026-07-23,historical_metadata_limited,"Earliest FINER-attributed source located in this search; bibliographic preview confirms edition metadata but the search did not prove first printed use or coinage"
-SRC-FINER-CURRENT,Werner and Willis,Back to the basics: guidance for formulating good research questions,Published 2023-10-12,current methods article,https://pmc.ncbi.nlm.nih.gov/articles/PMC11129835/,2026-07-23,current_primary,"Current discussion of FINER as a practical question-appraisal framework; novelty requires literature review"
-SRC-PLATT-1964,John R. Platt,Strong Inference,Published 1964-10-16,primary methods essay,https://www.science.org/doi/10.1126/science.146.3642.347,2026-07-23,foundational_primary,"Multiple alternatives, crucial experiments, and iterative exclusion; DOI 10.1126/science.146.3642.347"
-SRC-COS-PREREG,Center for Open Science,Preregistration,Current official page,official guidance,https://www.cos.io/initiatives/prereg,2026-07-23,current_official,"Separates planned from unplanned work and requires transparent changes; exploration remains valid"
-SRC-OSF-REG,Center for Open Science / OSF,Welcome to Registrations and Preregistrations,Current 2026 help page,official implementation guidance,https://help.osf.io/article/330-welcome-to-registrations,2026-07-23,current_official,"Timestamped plans, template guidance, analysis details, and anticipated deviations"
-SRC-COS-RR,Center for Open Science,Registered Reports,Current official initiative page,official guidance,https://www.cos.io/initiatives/registered-reports,2026-07-23,current_official,"Results-blind protocol review and in-principle acceptance; verify the target journal policy"
-SRC-SPIRIT-2025,SPIRIT-CONSORT Group,SPIRIT 2025 statement: updated guideline for protocols of randomised trials,Published 2025-04-28,primary reporting guideline,https://www.bmj.com/content/389/bmj-2024-081477,2026-07-23,current_primary,"34 minimum protocol items; supersedes SPIRIT 2013; DOI 10.1136/bmj-2024-081477"
-SRC-CONSORT-2025,SPIRIT-CONSORT Group,CONSORT 2025 statement: updated guideline for reporting randomised trials,Published 2025-04-14,primary reporting guideline,https://www.bmj.com/content/389/bmj-2024-081123,2026-07-23,current_primary,"30-item result-reporting guideline with open-science, harms, outcomes, intervention, and change-reporting updates"
-SRC-ICH-E9R1,International Council for Harmonisation,ICH E9(R1) Addendum on Estimands and Sensitivity Analysis in Clinical Trials,Step 4 2019; implemented 2020,official statistical guidance,https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_1203.pdf,2026-07-23,current_official,"Defines estimand as the precise treatment-effect target and aligns planning, design, analysis, sensitivity, and interpretation"
-SRC-WHATIF,Hernán and Robins,Causal Inference: What If,2020 citation; latest author-hosted revision linked 2025-11-21,foundational methods book,https://miguelhernan.org/whatifbook,2026-07-23,current_author_source,"Causal questions, counterfactuals, interventions, confounding, selection, causal diagrams, measurement, and target-trial emulation"
-SRC-NEG-CONTROL,Lipsitch Tchetgen Tchetgen and Cohen,Negative controls: a tool for detecting confounding and bias in observational studies,Published 2010-05,primary methods article,https://pubmed.ncbi.nlm.nih.gov/20335814/,2026-07-23,foundational_primary,"Negative exposure and outcome controls; DOI 10.1097/EDE.0b013e3181d61eeb"
-SRC-HARKING,Norbert L. Kerr,HARKing: hypothesizing after the results are known,Published 1998,primary methods article,https://pubmed.ncbi.nlm.nih.gov/15647155/,2026-07-23,foundational_primary,"Defines presenting a post hoc hypothesis as if a priori; DOI 10.1207/s15327957pspr0203_4"
-SRC-ASA-PVALUE,American Statistical Association,ASA Statement on Statistical Significance and P-Values,Released 2016-03-07,professional statistical statement,https://www.amstat.org/asa/files/pdfs/P-ValueStatement.pdf,2026-07-23,current_official,"Thresholds alone do not support scientific conclusions; p-values do not measure hypothesis truth or effect importance; full reporting is required"
-SRC-NASEM-RR,National Academies of Sciences Engineering and Medicine,Reproducibility and Replicability in Science,Published 2019-05-07,consensus report,https://www.nationalacademies.org/read/25303,2026-07-23,current_authoritative,"Defines reproducibility using same data/code and replicability using new data; DOI 10.17226/25303"
-SRC-TOP,Center for Open Science collaborators,Promoting an open research culture,Published 2015-06-26,primary transparency framework,https://www.science.org/doi/10.1126/science.aab2374,2026-07-23,current_primary,"Transparency and Openness Promotion guidelines; apply with privacy, consent, governance, and security limits"
-SRC-NIH-DMS,National Institutes of Health,Data Management and Sharing Policy,Effective 2023-01-25,official policy,https://sharing.nih.gov/data-management-and-sharing-policy,2026-07-23,current_official,"Prospective data-management and sharing planning for covered NIH-funded research; sharing remains subject to justified limits"
-SRC-NIST-GENAI,National Institute of Standards and Technology,Artificial Intelligence Risk Management Framework: Generative Artificial Intelligence Profile,NIST AI 600-1 July 2024; page updated 2026-04-08,official risk framework,https://www.nist.gov/publications/artificial-intelligence-risk-management-framework-generative-artificial-intelligence,2026-07-23,current_official,"Confabulation, privacy, harmful bias/homogenization, information integrity, dangerous recommendations, and human-AI configuration"
-SRC-DOSHI-HAUSER,Doshi and Hauser,Generative AI enhances individual creativity but reduces the collective diversity of novel content,Published 2024-07-12,primary research,https://www.science.org/doi/10.1126/sciadv.adn5290,2026-07-23,current_primary,"AI-assisted stories were more similar in this experiment; do not generalize beyond the studied task without evidence"
-SRC-UNESCO-AI,UNESCO,Recommendation on the Ethics of Artificial Intelligence,Adopted 2021; official page current 2026,international recommendation,https://www.unesco.org/en/artificial-intelligence/recommendation-ethics,2026-07-23,current_official,"Human rights, privacy, accountability, transparency, diversity, and human oversight"
-SRC-UNESCO-OPEN,UNESCO,Recommendation on Open Science,Adopted 2021,international recommendation,https://unesdoc.unesco.org/ark:/48223/pf0000379949,2026-07-23,current_official,"Open-science values and practices with responsibility, inclusiveness, and governance"
-SRC-HHS-COMMON-RULE,U.S. Department of Health and Human Services,Federal Policy for the Protection of Human Subjects (Common Rule),Official page updated 2026-01-15,regulation and policy index,https://www.hhs.gov/ohrp/regulations-and-policy/regulations/common-rule/index.html,2026-07-23,current_official,"45 CFR 46 applicability and agency implementation; obtain an authorized local determination"
-SRC-BELMONT,U.S. Department of Health and Human Services,The Belmont Report,Published 1979,ethical principles report,https://www.hhs.gov/ohrp/regulations-and-policy/belmont-report/index.html,2026-07-23,current_foundational,"Respect for persons, beneficence, and justice"
-SRC-HELSINKI,World Medical Association,WMA Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants,Revised October 2024,international ethical declaration,https://www.wma.net/policies-post/wma-declaration-of-helsinki/,2026-07-23,current_official,"Current international medical-research ethics statement; local law and review remain controlling"
-SRC-OLAW-PHS,Office of Laboratory Animal Welfare,Public Health Service Policy on Humane Care and Use of Laboratory Animals,Current official policy page,official animal-welfare policy,https://grants.nih.gov/policy-and-compliance/policy-topics/animal-welfare/laws-regulations/phs-policy,2026-07-23,current_official,"Institutional assurance and IACUC review for covered PHS-conducted or supported animal activities"
-SRC-ARRIVE,NC3Rs / ARRIVE Group,ARRIVE Guidelines 2.0,Published 2020,animal reporting guideline,https://arriveguidelines.org/arrive-guidelines,2026-07-23,current_official,"Reporting guidance for in vivo animal research; not an ethics approval or design-quality certificate"
-SRC-NIH-RSNA,National Institutes of Health,NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules,April 2024 or latest revision,official biosafety policy,https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.htm,2026-07-23,current_official,"Institutional biosafety oversight and covered research categories; verify the latest revision and local applicability"
-SRC-NIH-BIOSEC,NIH Office of Science Policy,Biosafety and Biosecurity Policy,Official page updated 2026-04-09,official policy portal,https://osp.od.nih.gov/policies/biosafety-and-biosecurity-policy,2026-07-23,current_official,"Current NIH biosafety, biosecurity, IBC, transparency, and Executive Order implementation links"
-SRC-BMBL,Centers for Disease Control and Prevention and National Institutes of Health,Biosafety in Microbiological and Biomedical Laboratories,6th edition June 2020,official biosafety guidance,https://www.cdc.gov/labs/bmbl/index.html,2026-07-23,current_official,"Risk assessment and biosafety guidance; use qualified institutional review rather than inferring procedures from this skill"
-SRC-WHO-LIFE,World Health Organization,Global Guidance Framework for the Responsible Use of the Life Sciences,Published 2022-09-13,international guidance,https://www.who.int/publications/i/item/9789240056107,2026-07-23,current_official,"Values, principles, tools, and governance for biorisks and dual-use throughout the research lifecycle"
-SRC-EO-14292,The White House,Executive Order 14292: Improving the Safety and Security of Biological Research,Signed 2025-05-05,executive order,https://www.whitehouse.gov/presidential-actions/2025/05/improving-the-safety-and-security-of-biological-research,2026-07-23,current_official,"Directed revision/replacement of 2024 DURC/PEPP policy and pause/termination actions for covered dangerous gain-of-function research"
-SRC-NIH-NOT-25-112,National Institutes of Health,NOT-OD-25-112: Implementation Update—Improving the Safety and Security of Biological Research,Issued 2025-05,official funding notice,https://grants.nih.gov/grants/guide/notice-files/NOT-OD-25-112.html,2026-07-23,current_official,"States Executive Order definitions superseded NIH's 2024 DURC/PEPP implementation and rescinds NOT-OD-25-061"
-SRC-ASPR-DURC,U.S. Department of Health and Human Services ASPR,Dual Use Research of Concern Oversight Policy Framework,Official page current at verification,official policy status page,https://aspr.hhs.gov/S3/Pages/Dual-Use-Research-of-Concern-Oversight-Policy-Framework.aspx,2026-07-23,current_transition_notice,"At verification, states the 2024 DURC/PEPP policy will be revised or replaced and page will update when revised policy is available"

package/skills/hypothesis-generation/references/causal_inference_and_claims.md

@@ -1,190 +0,0 @@
-# Causal Inference and Claim Discipline
-
-## Start with the scientific target
-
-Association, prediction, intervention effects, and mechanisms answer different questions:
-
-- **Descriptive:** What is the distribution or pattern?
-- **Associational:** How do measured variables co-vary in the observed data?
-- **Predictive:** How well does information predict outcomes in a target setting?
-- **Causal:** What would differ under specified interventions or exposure conditions?
-- **Mechanistic:** Through which process would the causal change occur?
-
-A model can predict accurately without identifying a causal effect. A randomized effect estimate can identify an intervention contrast without establishing the complete mechanism.
-
-## Define a causal estimand
-
-Following the causal-question and ICH E9(R1) principles where applicable, specify:
-
-1. **Population/system:** To whom or what does the contrast apply?
-2. **Intervention/exposure:** What condition is set, assigned, or contrasted?
-3. **Comparator:** What alternative condition is compared?
-4. **Outcome:** What variable is affected and how is it measured?
-5. **Time horizon:** When is the outcome assessed?
-6. **Population summary:** Mean difference, risk ratio, quantile contrast, survival summary, or another target.
-7. **Intercurrent events:** How are post-assignment events handled when they affect interpretation or measurement?
-8. **Treatment versions:** Are interventions sufficiently well defined?
-
-The estimand should exist before choosing an estimator or model.
-
-## Counterfactual contrast
-
-Causal effects compare outcomes under different conditions for the same target units, although both conditions cannot usually be observed for one unit. Identification therefore depends on design and assumptions.
-
-For observational data, state:
-
-- target-trial analogue or other design logic;
-- consistency/well-defined intervention assumptions;
-- exchangeability/no-unmeasured-confounding assumptions;
-- positivity/overlap;
-- interference assumptions;
-- measurement and missingness assumptions;
-- model assumptions introduced by estimation.
-
-Do not write “controlled for confounding” as if adjustment proves exchangeability.
-
-## Bias pathways
-
-### Confounding
-
-A common cause of exposure/intervention and outcome can create or obscure an association. Address through design, randomization where ethical/feasible, restriction, matching, measurement and adjustment of justified common causes, negative controls, sensitivity analysis, or triangulation.
-
-Risks:
-
-- unmeasured or poorly measured common causes;
-- time-varying confounders affected by prior treatment;
-- inappropriate adjustment for instruments, mediators, or colliders;
-- residual confounding after coarse categorization.
-
-### Selection bias
-
-Selection into the sample, analysis, follow-up, or observed outcome can depend on causes of exposure and outcome. Record:
-
-- sampling and eligibility;
-- participation and consent;
-- exclusions;
-- attrition and censoring;
-- complete-case restrictions;
-- availability of measurements;
-- conditioning introduced by data linkage.
-
-### Collider bias
-
-A collider is a common effect of two variables. Conditioning on it or its descendant can open a non-causal path. Common sources include:
-
-- selection into a study or subgroup;
-- restricting to diagnosed, hospitalized, tested, or surviving participants;
-- adjusting for a post-exposure variable affected by another cause of the outcome;
-- using complete cases when missingness is jointly caused.
-
-More covariates are not automatically better.
-
-### Reverse causation
-
-The outcome or its precursors may influence the exposure or measurement. Cross-sectional order is especially weak evidence of direction. Use temporal design, lagged measurements, incident outcomes, intervention, negative controls, or explicit bidirectional candidates where appropriate.
-
-### Measurement bias
-
-Measurement error can:
-
-- attenuate or inflate estimates;
-- differ by exposure or outcome;
-- induce apparent interactions;
-- distort covariate adjustment;
-- affect selection into analysis.
-
-Operationalization and validation are part of causal design, not a later documentation task.
-
-## Mediators and effect modifiers
-
-- A **mediator** lies on a causal pathway. Adjusting for it changes the target from total to a direct or controlled effect and introduces additional assumptions.
-- An **effect modifier** describes variation in a causal contrast across strata. It is not synonymous with statistical interaction in every scale.
-- A **confounder** is defined relative to a target causal contrast and design, not simply by association with the outcome.
-
-Label the intended role before analysis and justify it with domain knowledge and a causal structure.
-
-## Negative controls
-
-Lipsitch, Tchetgen Tchetgen, and Cohen distinguish negative-control exposures and outcomes:
-
-- A negative-control exposure should not cause the target outcome through the proposed mechanism but should share relevant confounding/bias pathways.
-- A negative-control outcome should not be caused by the target exposure through the proposed mechanism but should share relevant bias pathways.
-
-Specify:
-
-- why the target mechanism cannot operate;
-- which biases should be shared;
-- expected result;
-- implication of control failure;
-- alternative reasons for a non-null control result.
-
-Negative controls detect some biases under assumptions; they do not prove absence of bias.
-
-## Claim-language rules
-
-### Associational
-
-Use:
-
-- “was associated with”;
-- “co-varied with”;
-- “predicted in the evaluated dataset”;
-- “the adjusted association.”
-
-State design, population, timing, effect/summary measure, uncertainty, and limitations.
-
-### Causal
-
-Use causal verbs only when:
-
-- the causal estimand is explicit;
-- design/identification logic is stated;
-- assumptions and sensitivity are visible;
-- confounding, selection, collider, reverse-causation, and measurement risks are addressed;
-- language is calibrated to the evidence.
-
-For observational work, “estimated causal effect under the stated assumptions” is often more accurate than an unqualified causal declaration.
-
-### Mechanistic
-
-Distinguish:
-
-- direct evidence for process steps;
-- mediation or intermediate measurements;
-- perturbation/rescue evidence;
-- temporal ordering;
-- analogy or plausibility only.
-
-A causal intervention effect does not by itself verify the proposed pathway.
-
-## Markdown claim annotations
-
-The bundled linter recognizes line-level annotations:
-
-```markdown
-[claim:associational] Exposure X was associated with outcome Y in the observed cohort.
-
-[claim:causal][estimand:E1][identification:observational_assumption_dependent][confounding:unresolved][selection:assessed][collider:assessed][reverse-causation:assessed] Under the stated assumptions, intervention X would reduce outcome Y over 12 months.
-```
-
-Allowed risk states are `assessed`, `unresolved`, and `not_applicable`. “Assessed” records that a human evaluation exists; it does not mean the risk is absent.
-
-Run:
-
-```bash
-python3 scripts/lint_causal_claims.py local-draft.md
-```
-
-The linter is lexical. It can miss causal language, flag benign phrases, and cannot judge whether a design identifies an effect.
-
-## Intervention-trial context
-
-For intervention hypotheses:
-
-- align objectives, estimands, outcomes, timing, harms, and analysis;
-- use SPIRIT 2025 for protocol reporting and CONSORT 2025 for trial-result reporting;
-- preserve access to protocol and statistical analysis plan;
-- report important post-start changes and non-prespecified outcomes/analyses;
-- include harms and participant/public involvement where applicable.
-
-Reporting completeness is not proof of ethical approval, design validity, regulatory compliance, or treatment efficacy.

package/skills/hypothesis-generation/references/concepts_and_workflow.md

@@ -1,173 +0,0 @@
-# Concepts and Candidate Lifecycle
-
-## Purpose
-
-This reference prevents common category errors in hypothesis work. It is a vocabulary and workflow guide, not a theory of confirmation and not an automatic ranking method.
-
-## Object model
-
-### Observation
-
-A bounded account of what was detected or reported:
-
-- source or measurement;
-- population/system, place, and time;
-- unit of observation;
-- preprocessing, exclusions, missingness, and uncertainty;
-- whether the observation was expected or selected after inspection.
-
-An observation can be mistaken, biased, or unrepresentative. It does not explain itself.
-
-### Research question
-
-An answerable question that fixes the scope of inquiry. It should identify the target population/system, variables or interventions, comparator where meaningful, outcome, timeframe, context, and claim type.
-
-PICO/PICOT is appropriate for many intervention-effect questions. It is not a universal ontology. Use a framework matched to the question and involve affected stakeholders where appropriate.
-
-### Hypothesis
-
-A candidate proposition that could explain or relate observations and yield testable implications. Keep its status as `candidate` until evidence changes the state. Avoid “validated hypothesis,” “proven mechanism,” and similar language unless the statement is being used only to quote a source accurately.
-
-### Mechanism
-
-A proposed process connecting antecedent conditions to an outcome. A mechanism should identify entities, activities, ordering, and boundary conditions where the domain permits. A plausible narrative without discriminating predictions remains a story.
-
-### Causal estimand
-
-A precise target causal contrast. At minimum, state:
-
-- target population/system;
-- intervention/exposure and comparator;
-- outcome and time horizon;
-- population-level summary;
-- treatment versions and intercurrent-event strategy where relevant;
-- identification assumptions.
-
-The estimand is the target, the estimator is the method, and the estimate is the numerical result.
-
-### Prediction
-
-An observable implication derived from a candidate before checking the target result. A useful prediction specifies conditions, measurement, expected pattern, uncertainty, and an incompatible result. It should distinguish at least one rival when possible.
-
-### Alternative explanation
-
-A rival account that could produce the same observation. Rivals include:
-
-- distinct mechanisms;
-- measurement or processing artifacts;
-- confounding/common causes;
-- selection or attrition;
-- collider conditioning;
-- reverse causation;
-- contextual or temporal heterogeneity;
-- stochastic variation.
-
-Rivals can coexist. Do not force mutual exclusivity when a mixed explanation is scientifically plausible.
-
-### Null hypothesis
-
-A defined no-effect/no-difference model used in an analysis. It is not “nothing happened,” and failure to reject it does not establish equivalence or absence. Define compatibility, equivalence, or non-inferiority rules separately when those are the scientific targets.
-
-### Negative control
-
-A control in which the target mechanism should not operate but relevant bias pathways should remain. Negative exposure and negative outcome controls can reveal confounding, selection, measurement, or analytic bias when their assumptions are credible. A negative control does not repair bias automatically.
-
-### Operationalization
-
-The mapping from a construct to a measurement, category, intervention, or variable. Record instrument/method, unit, timing, population/system, validity, reliability, calibration, missingness, transformations, cut points, and limitations.
-
-### Analysis plan
-
-The planned mapping from data to estimand, prediction, or descriptive target. It includes units, populations, transformations, models, contrasts, effect measures, uncertainty, missingness, multiplicity, diagnostics, sensitivity analyses, and decision rules.
-
-### Evidence
-
-Empirical observations or documented sources that bear on claims. Record whether a source supports, challenges, contextualizes, or supplies a method. Citation presence does not prove claim support; a human must inspect the source.
-
-## Candidate lifecycle
-
-Use explicit states:
-
-1. **Draft candidate** — generated but not yet searched or operationalized.
-2. **Evidence-bounded candidate** — linked to a dated search and source ledger.
-3. **Test-ready candidate** — has measurements, rivals, falsifiers, controls, and analysis links.
-4. **Preregistered candidate** — time-stamped before the relevant outcome was inspected.
-5. **Tested candidate** — results and deviations are available.
-6. **Retained, revised, challenged, or unresolved** — human interpretation with uncertainty.
-
-Never use `true`, `proven`, or `selected_winner` as a machine-generated state.
-
-## Multiple hypotheses and strong inference
-
-Platt’s 1964 strong-inference essay advocates:
-
-1. devising alternative hypotheses;
-2. devising a crucial experiment with alternative possible outcomes that exclude candidates;
-3. performing the experiment cleanly;
-4. recycling the process with subhypotheses.
-
-Use this as a discipline for contrast, not as a guarantee of truth. In practice:
-
-- alternatives may be incomplete;
-- candidates may not be mutually exclusive;
-- auxiliary assumptions can fail;
-- measurements may not distinguish the intended mechanisms;
-- a “crucial” result may be indeterminate;
-- exclusions remain provisional.
-
-Always include an “unknown or mixed explanation” path in interpretation.
-
-## Exploratory and confirmatory modes
-
-### Exploratory
-
-- Generates observations, candidates, variables, and models.
-- Can be data-dependent.
-- Must record that dependence.
-- Produces hypotheses for future tests rather than relabeling the same-data analysis as confirmation.
-
-### Confirmatory
-
-- Defines hypotheses, outcomes, exclusions, transformations, models, and decision rules before inspecting the target result.
-- Preserves the planned analysis.
-- Reports deviations and additional analyses transparently.
-
-Both modes are scientifically valuable. The integrity failure is not exploration; it is presenting exploration as if it were prespecified.
-
-## Uncertainty vocabulary
-
-Prefer:
-
-- “candidate explanation”;
-- “consistent with under the stated assumptions”;
-- “challenges this candidate if measurement and design assumptions hold”;
-- “not distinguished by this result”;
-- “not located within the documented search boundary”;
-- “requires replication or external validation.”
-
-Avoid:
-
-- “proved” or “disproved” for ordinary empirical results;
-- “novel” based only on no quick search hit;
-- “no effect” from a non-significant result;
-- “causes” from an unqualified association;
-- “the mechanism” when several remain plausible.
-
-## Minimum handoff
-
-A hypothesis package should contain:
-
-- frozen observation;
-- framed question and claim type;
-- dated search boundary and source ledger;
-- candidate hypotheses and mechanisms;
-- rivals and bias explanations;
-- causal estimand if applicable;
-- discriminating predictions and falsifiers;
-- operationalization and measurement-validity record;
-- nulls and controls;
-- design and analysis plan;
-- uncertainty and boundary conditions;
-- ethics/safety/regulatory gates;
-- preregistration/deviation plan;
-- accountable human review.

package/skills/hypothesis-generation/references/ethics_safety_and_ai.md

@@ -1,216 +0,0 @@
-# Ethics, Safety, Feasibility, and Responsible AI
-
-## This is a routing guide
-
-This reference helps identify gates. It is not legal, medical, regulatory, biosafety, biosecurity, export-control, ethics, or institutional advice. Requirements vary by jurisdiction, sponsor, institution, organism, material, and intended use.
-
-When applicability is uncertain, mark the gate `undetermined`, stop operational planning, and obtain a determination from the qualified local authority.
-
-## Universal intake
-
-Record:
-
-- accountable owner and institution;
-- intended purpose and foreseeable misuse;
-- affected people, animals, communities, ecosystems, infrastructure, or security interests;
-- data and material sensitivity;
-- funding, jurisdiction, and collaborating sites;
-- required expertise;
-- conflicts and incentives;
-- approvals, determinations, and unresolved blocks;
-- less risky ways to answer the question.
-
-Feasibility never overrides ethics or safety.
-
-## Human-participant gate
-
-Potential triggers include:
-
-- intervention or interaction with living people;
-- identifiable private information or biospecimens;
-- secondary use, linkage, re-identification, recruitment, or contact;
-- vulnerable populations or sensitive topics;
-- international or community-governed data.
-
-Required action:
-
-- obtain an IRB/REC or other authorized determination before research starts;
-- do not self-declare exemption;
-- address consent or authorized waiver, privacy, security, equitable selection, risk/benefit, compensation, return of results, and community governance as applicable;
-- use additional protections required by law or policy.
-
-In the United States, HHS 45 CFR 46 includes the Common Rule and additional subparts. Local and non-U.S. rules can differ. The 2024 revision of the World Medical Association Declaration of Helsinki is a relevant international ethical statement for medical research involving human participants.
-
-This skill does not provide clinical advice or authorize an intervention.
-
-## Animal-research gate
-
-Potential triggers include live vertebrate animals, field capture, breeding, procedures, tissues tied to ongoing animal activities, or covered training/testing.
-
-Required action:
-
-- obtain the applicable IACUC or equivalent approval before work;
-- establish institutional assurance and veterinary oversight where required;
-- apply replacement, reduction, and refinement;
-- justify species/model, numbers, endpoints, welfare monitoring, analgesia/anesthesia, and humane endpoints through the authorized process;
-- use current reporting guidance such as ARRIVE when applicable.
-
-The bundled tools do not calculate animal numbers or approve protocols.
-
-## Biosafety and biosecurity gate
-
-Potential triggers include:
-
-- recombinant or synthetic nucleic acids;
-- infectious agents, toxins, biological materials, gene transfer, or modified organisms;
-- environmental release;
-- select agents or regulated materials;
-- procedures that could alter hazard, host range, pathogenicity, transmissibility, resistance, or detection;
-- work beyond established institutional containment and training.
-
-Required action:
-
-- stop before operational detail;
-- route to the biosafety officer, Institutional Biosafety Committee, and other required authority;
-- use the current NIH Guidelines, CDC/NIH *Biosafety in Microbiological and Biomedical Laboratories*, local biosafety manual, and applicable regulations;
-- document containment and occupational-health decisions only after authorized review.
-
-Do not infer a containment level or operating procedure from this skill.
-
-## Dual-use and harmful-use gate
-
-Potential triggers include research, data, models, or protocols that could reasonably enable:
-
-- increased biological harm or spread;
-- evasion of detection, treatment, control, or safeguards;
-- scalable production or dissemination of harmful agents;
-- weaponization;
-- exploitation of critical vulnerabilities;
-- transfer of restricted technical information.
-
-Required action:
-
-1. Do not provide optimization, stepwise procedures, parameter choices, sequences, acquisition pathways, or troubleshooting that increase harmful capability.
-2. Preserve only a high-level scientific question, benefit rationale, and risk statement.
-3. Route to institutional dual-use/biosecurity review, funder, legal/export-control, and other required authorities.
-4. Follow current policy, award terms, and jurisdiction-specific controls.
-
-### U.S. policy status checked 2026-07-23
-
-- Executive Order 14292 of May 5, 2025 directed revision/replacement of the 2024 U.S. Government DURC/PEPP policy and paused federally funded research meeting its “dangerous gain-of-function” definition pending the replacement policy.
-- NIH Notice NOT-OD-25-112 stated that the Executive Order superseded NIH implementation of the 2024 DURC/PEPP policy and rescinded NOT-OD-25-061.
-- The HHS/ASPR policy page still stated at the verification date that federal departments and agencies would revise or replace the 2024 policy and that the page would be updated when the revised policy became available.
-
-Do not use the superseded 2024 implementation as current clearance. Recheck the official policy and award terms for every project because this status is time-sensitive.
-
-WHO’s *Global Guidance Framework for the Responsible Use of the Life Sciences* provides an international risk-governance framework; it does not replace national or local rules.
-
-## Data-governance gate
-
-Before using data:
-
-- confirm authority, consent, license, data-use agreement, and purpose limitation;
-- classify sensitivity and re-identification risk;
-- minimize fields and access;
-- use approved storage, retention, deletion, audit, and sharing controls;
-- address community and Indigenous governance;
-- separate public, controlled, confidential, proprietary, and export-controlled materials.
-
-Passing a local schema check is not de-identification, anonymization, HIPAA compliance, GDPR compliance, or authorization to share.
-
-## Regulatory gate
-
-Potential triggers include:
-
-- human interventions or clinical investigations;
-- drugs, biologics, devices, diagnostics, or software intended for clinical use;
-- environmental release;
-- genetically modified organisms;
-- regulated laboratory, animal, agricultural, or chemical activities;
-- claims intended for product labeling, approval, or public-health action.
-
-Record:
-
-- intended use;
-- jurisdiction;
-- product/activity classification;
-- sponsor and responsible regulatory owner;
-- applicable quality system or submission route;
-- current determination and source/date.
-
-Do not infer regulatory status from a research label, reporting checklist, or generated artifact.
-
-## Feasibility gate
-
-Assess:
-
-- scientific and technical capability;
-- validated measurement;
-- statistical information/precision;
-- qualified personnel and facilities;
-- time and resources;
-- access to population/system;
-- approvals and material/data access;
-- foreseeable failure and stopping criteria.
-
-If infeasible, revise the question or conduct a bounded feasibility study. Do not weaken protections or invent optimistic assumptions.
-
-## Responsible AI policy
-
-### Local-first rule
-
-Default to local processing. Do not send sensitive, unpublished, confidential, personal, proprietary, controlled, or security-relevant information to an external AI system without:
-
-- explicit authorization;
-- a named approved service and account;
-- a defined minimum data scope;
-- contract, retention, training-use, location, and access review;
-- applicable publisher, funder, institutional, and participant permission.
-
-The bundled scripts make no network, model, image, or external-service calls and read no environment credentials.
-
-### Human accountability
-
-An accountable human must:
-
-- own the question, candidate set, and final scientific decisions;
-- verify every citation, identifier, quotation, and source-to-claim link;
-- verify calculations and scientific plausibility;
-- inspect omitted rivals and boundary conditions;
-- review ethics, safety, privacy, dual-use, and regulatory implications;
-- disclose AI assistance where policy requires;
-- retain or delete records under the controlling policy.
-
-AI output is not evidence and cannot grant approval.
-
-### Known AI risks
-
-NIST AI 600-1 identifies generative-AI risks including confabulation, data privacy, harmful bias/homogenization, information integrity, human–AI configuration, and dangerous recommendations. Mitigate by:
-
-- independent human ideation before AI expansion;
-- generating rivals from different disciplinary perspectives;
-- separating source retrieval from claim synthesis;
-- checking primary sources directly;
-- recording prompts/tool versions when authorized and scientifically relevant;
-- challenging convergent, polished, or overly confident output;
-- using multiple human reviewers for high-consequence work.
-
-Doshi and Hauser’s 2024 experiment found AI-assisted stories were more similar to one another even while some individual creativity measures improved. Do not generalize that one study to all scientific ideation; treat homogenization as a plausible risk and preserve independent candidate generation.
-
-UNESCO’s AI ethics recommendation emphasizes human rights, privacy/data protection, responsibility/accountability, transparency, and human oversight. Ultimate responsibility remains human.
-
-## Stop conditions
-
-Stop and escalate when:
-
-- authorization is absent or ambiguous;
-- a required review is missing;
-- data or material classification is unknown;
-- harmful-use potential cannot be bounded;
-- a request seeks operational harmful detail;
-- patient-specific advice is requested;
-- a regulatory or legal determination is needed;
-- the proposed measurement cannot validly bear on the construct;
-- qualified expertise is unavailable.
-
-Record the block without copying sensitive details into a general-purpose artifact.