medsci-skills 4.1.0

package/skills/write-protocol/references/ethics_checklist.md

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+# Ethics Checklist for Research Protocols
+
+Use this checklist when completing Section 7 (Ethical Considerations) of a research
+protocol. Check all items that apply and document compliance for each.
+
+---
+
+## Universal Requirements
+
+These apply to all research involving human subjects, regardless of jurisdiction.
+
+- [ ] IRB/Ethics committee approval obtained or submitted
+- [ ] Informed consent process documented (or waiver justification provided)
+- [ ] Data privacy and protection measures described
+- [ ] Conflict of interest disclosed for all investigators
+- [ ] Vulnerable populations considerations addressed (if applicable: minors, pregnant women, prisoners, cognitively impaired)
+- [ ] Data sharing and retention policy documented
+- [ ] Adverse event reporting plan (for interventional studies)
+- [ ] Study stopping rules defined (for interventional studies)
+- [ ] Data Safety Monitoring Board established (if required)
+- [ ] Insurance or compensation for research-related injury (if applicable)
+
+---
+
+## Retrospective Study Considerations
+
+For chart review and retrospective cohort studies:
+
+- [ ] Waiver of informed consent justified (minimal risk, impracticable to obtain)
+- [ ] De-identification plan documented (Safe Harbor or Expert Determination method)
+- [ ] Access to medical records limited to authorized study personnel
+- [ ] No direct patient contact required (or contact plan approved)
+- [ ] Data linkage procedures documented (if combining multiple databases)
+
+---
+
+## Jurisdiction-Specific: Korea
+
+### Personal Information Protection Act (PIPA)
+
+- [ ] Personal information collection purpose specified
+- [ ] Minimum necessary data principle applied
+- [ ] Consent obtained or exemption justified under PIPA Article 58
+- [ ] Data processing records maintained
+- [ ] Cross-border data transfer plan documented (if applicable)
+
+### Bioethics and Safety Act
+
+- [ ] Institutional Bioethics Committee (IBC) review completed
+- [ ] Human subject research approval obtained
+- [ ] Genetic information handling compliant (if applicable)
+- [ ] Biobank regulations followed (if using stored specimens)
+
+### Multi-Center Studies
+
+- [ ] Ministry of Health and Welfare (MOHW) notification submitted
+- [ ] Each participating institution's IRB approval obtained
+- [ ] Central IRB designation documented (if applicable)
+
+### Clinical Trials
+
+- [ ] Clinical Research Information Service (CRIS) registration completed
+- [ ] MFDS approval obtained (if investigational drug/device)
+- [ ] Good Clinical Practice (KGCP) compliance documented
+
+---
+
+## Jurisdiction-Specific: United States
+
+### HIPAA Privacy Rule
+
+- [ ] HIPAA authorization obtained from participants, OR
+- [ ] Waiver of HIPAA authorization approved by IRB (all 4 criteria met):
+  - [ ] Research involves no more than minimal risk to privacy
+  - [ ] Research could not practicably be conducted without the waiver
+  - [ ] Research could not practicably be conducted without access to PHI
+  - [ ] Privacy risks are reasonable relative to anticipated benefits
+- [ ] Limited data set with Data Use Agreement (if applicable)
+- [ ] Business Associate Agreement in place (if third-party data handling)
+
+### Common Rule (45 CFR 46)
+
+- [ ] IRB review category determined: exempt, expedited, or full board
+- [ ] Informed consent elements documented (8 required, 6 additional as applicable)
+- [ ] Continuing review schedule established (if full board)
+- [ ] Unanticipated problem reporting plan in place
+
+### Registration and Reporting
+
+- [ ] ClinicalTrials.gov registration completed (if applicable trial)
+- [ ] FDA IND/IDE obtained (if investigational drug or device)
+- [ ] NIH data sharing plan submitted (if NIH-funded)
+
+---
+
+## Jurisdiction-Specific: European Union
+
+### GDPR Article 9 (Health Data)
+
+- [ ] Lawful basis for health data processing identified:
+  - [ ] Explicit consent (Article 9(2)(a)), OR
+  - [ ] Scientific research with appropriate safeguards (Article 9(2)(j))
+- [ ] Data Protection Impact Assessment (DPIA) completed (if high-risk processing)
+- [ ] Data Protection Officer (DPO) consulted
+- [ ] Data processing records maintained (Article 30)
+- [ ] Data subject rights procedures established (access, rectification, erasure)
+
+### Cross-Border Data Transfer
+
+- [ ] Adequacy decision exists for receiving country, OR
+- [ ] Standard Contractual Clauses in place, OR
+- [ ] Binding Corporate Rules applied
+- [ ] Transfer Impact Assessment completed
+
+### Clinical Trials Regulation (EU 536/2014)
+
+- [ ] EudraCT / CTIS registration completed
+- [ ] National competent authority authorization obtained
+- [ ] Ethics committee opinion obtained
+- [ ] Sponsor responsibilities documented
+
+---
+
+## AI-Specific Considerations
+
+For studies involving artificial intelligence or machine learning:
+
+- [ ] AI tool role disclosed in the protocol (development, validation, clinical decision support)
+- [ ] Algorithm transparency and explainability statement included
+- [ ] Training data provenance and consent status documented
+- [ ] Bias mitigation strategy described (demographic, selection, measurement bias)
+- [ ] Human oversight of AI decisions described (who reviews, when, how)
+- [ ] AI failure modes and fallback procedures documented
+- [ ] Model versioning and reproducibility plan in place
+- [ ] Post-deployment monitoring plan described (if applicable)
+- [ ] Patient notification about AI involvement (if direct clinical use)
+- [ ] Regulatory classification of AI/ML tool determined (SaMD, if applicable)
+
+---
+
+## Checklist Usage Notes
+
+1. Not all items apply to every study. Check only those relevant to your study type
+   and jurisdiction.
+2. When in doubt, consult your institutional IRB office. Requirements vary across
+   institutions even within the same jurisdiction.
+3. Keep a dated copy of this checklist in your study files as documentation of
+   ethical considerations reviewed.
+4. Update the checklist if the protocol undergoes amendments that affect ethical
+   considerations.

package/skills/write-protocol/references/protocol_template.md

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+# Research Protocol Template
+
+Complete 10-section structure for IRB/ethics committee submission.
+Use this template as a formatting reference when generating protocol drafts.
+
+---
+
+## Header
+
+```
+Research Protocol
+
+Title: [Full study title]
+Short Title: [Acronym or abbreviated title]
+Protocol Version: [e.g., 1.0]
+Date: [YYYY-MM-DD]
+Principal Investigator: [Name, Degree, Affiliation]
+Co-Investigators: [Names, Degrees, Affiliations]
+Institution: [Institution name and department]
+```
+
+---
+
+## 1. Background and Rationale
+
+**Target length**: 400-600 words
+**Format**: Full prose paragraphs, no bullet points
+
+### Content guidance
+
+**Paragraph 1 -- Clinical context (100-150 words)**
+- Describe the disease or clinical problem
+- State the burden (incidence, prevalence, morbidity, mortality)
+- Describe current clinical practice or standard of care
+
+Example phrasing:
+> "[Disease] affects approximately [N] patients annually worldwide and remains a
+> significant cause of [morbidity/mortality]. Current standard of care involves
+> [intervention/diagnostic approach], which [limitation]."
+
+**Paragraph 2 -- Literature review (150-200 words)**
+- Summarize key prior studies (3-5 references minimum)
+- Identify what is known and what remains uncertain
+- Highlight the specific knowledge gap this study addresses
+
+Example phrasing:
+> "Several studies have investigated [topic]. [Author] et al. reported [finding]
+> in a [study type] of [N] patients (DOI: [verified DOI]). However, [limitation
+> of prior work]. To date, no study has [specific gap]."
+
+**Paragraph 3 -- Rationale and hypothesis (100-150 words)**
+- State why this study is needed
+- Describe what this study will add
+- Present the hypothesis or research question
+
+Example phrasing:
+> "This study aims to [objective]. We hypothesize that [specific, testable
+> hypothesis]. The results of this study will [clinical or scientific impact]."
+
+### What to avoid
+- Overly broad introductions unrelated to the research question
+- Unsupported claims or citations without DOI/PMID
+- AI-pattern phrases: "it is worth noting", "plays a crucial role", "comprehensive"
+
+---
+
+## 2. Study Design and Eligibility Criteria
+
+**Target length**: 300-500 words
+**Format**: Full prose with numbered criteria lists
+
+### Content guidance
+
+**Study design statement (50-80 words)**
+
+Example phrasing:
+> "This is a [retrospective/prospective] [cohort/cross-sectional/case-control/
+> diagnostic accuracy] study conducted at [institution]. This design was selected
+> because [justification -- e.g., the outcome has already occurred and medical
+> records are available, or a prospective comparison is needed to minimize bias]."
+
+**Setting and study period (30-50 words)**
+
+> "The study will be conducted at [institution name], a [bed count]-bed
+> [academic/community] [hospital/medical center] in [city, country]. The study
+> period spans from [start date] to [end date]."
+
+**Inclusion criteria (numbered list)**
+
+> Patients will be included if they meet all of the following criteria:
+> 1. Age >= [X] years at the time of [index event]
+> 2. [Diagnosis/procedure/exposure] confirmed by [method]
+> 3. [Imaging/lab/clinical data] available within [timeframe]
+> 4. [Additional criterion as needed]
+
+**Exclusion criteria (numbered list)**
+
+> Patients will be excluded if any of the following apply:
+> 1. [Condition that would confound results]
+> 2. [Missing critical data -- specify which variables]
+> 3. [Prior treatment that alters the natural history]
+> 4. [Additional criterion as needed]
+
+### What to avoid
+- Vague inclusion criteria (e.g., "patients with cancer" without specifying type, stage, or confirmation method)
+- Overly restrictive criteria that limit generalizability without justification
+- Missing the analysis unit declaration (patient vs lesion vs exam)
+
+---
+
+## 3. Sample Size Justification
+
+**Target length**: 150-300 words
+**Format**: Full prose, single paragraph or two short paragraphs
+
+### Content guidance
+
+State all of the following:
+- Statistical test used for sample size calculation
+- Expected effect size and its source (prior study with citation)
+- Alpha level (typically 0.05, two-sided)
+- Power (typically 0.80 or 0.90)
+- Attrition or dropout adjustment (typically 10-20%)
+- Final enrollment target
+
+Example phrasing:
+> "Sample size was calculated based on [test type]. Based on prior data from
+> [Author] et al. (DOI: [verified DOI]), we assumed [effect size specification --
+> e.g., a difference of X% between groups, an AUC of 0.85 under the alternative
+> hypothesis]. With a two-sided alpha of 0.05 and 80% power, [N] subjects per
+> group are required. Accounting for an anticipated [X]% attrition rate, we plan
+> to enroll [N_adjusted] participants in total."
+
+For diagnostic accuracy studies:
+> "Using the method of [Flahault/Buderer/Obuchowski], assuming a target
+> sensitivity of [X]% with a 95% confidence interval lower bound no less than
+> [Y]%, and an expected prevalence of [Z]%, a minimum of [N] subjects is required."
+
+### What to avoid
+- Missing the source of the assumed effect size
+- Power < 0.80 without explicit justification
+- Failure to account for attrition or clustering
+
+---
+
+## 4. Statistical Analysis Plan
+
+**Target length**: 300-500 words
+**Format**: Full prose with structured subsections
+
+### Content guidance
+
+**Descriptive statistics (40-60 words)**
+
+> "Continuous variables will be reported as mean (standard deviation) or median
+> (interquartile range) depending on normality assessed by the Shapiro-Wilk test.
+> Categorical variables will be reported as frequency (percentage)."
+
+**Primary analysis (80-120 words)**
+
+> "The primary outcome [outcome name] will be compared between [groups] using
+> [specific test]. [State assumptions and how violations will be handled -- e.g.,
+> if the normality assumption is violated, the Wilcoxon rank-sum test will be
+> used as an alternative.] Results will be reported as [effect measure] with 95%
+> confidence intervals."
+
+For diagnostic accuracy:
+> "Sensitivity, specificity, positive predictive value, and negative predictive
+> value will be calculated with exact binomial 95% confidence intervals. The area
+> under the receiver operating characteristic curve (AUC) will be estimated using
+> [DeLong/bootstrap] method."
+
+**Secondary analyses (60-80 words)**
+
+> "Secondary outcomes will be analyzed as follows: [list each secondary outcome
+> and its corresponding test]. These analyses are considered exploratory and will
+> not be adjusted for multiple comparisons unless otherwise specified."
+
+**Subgroup analyses (40-60 words)**
+
+> "Pre-specified subgroup analyses will be conducted by [variables -- e.g., age
+> group, sex, disease severity]. Interaction terms will be tested in regression
+> models to assess effect modification. Subgroup results will be interpreted with
+> caution given the reduced statistical power."
+
+**Missing data (40-60 words)**
+
+> "The extent and pattern of missing data will be assessed. If missing data
+> exceed [X]%, [multiple imputation / inverse probability weighting] will be
+> applied. A complete-case sensitivity analysis will be conducted to assess the
+> robustness of results."
+
+**Software and significance level (20-30 words)**
+
+> "All analyses will be performed using [R version X.X.X / Python X.X / SAS X.X].
+> A two-sided p-value < 0.05 will be considered statistically significant."
+
+### What to avoid
+- Listing tests without connecting them to specific outcomes
+- Missing the missing data strategy
+- Unspecified software version
+- "Appropriate statistical tests will be used" (too vague)
+
+---
+
+## 5. Study Title and Registration
+
+**Format**: TODO markers only
+
+```
+[TODO: Full study title]
+[TODO: Short title / acronym]
+[TODO: Clinical trial registry number if applicable (e.g., ClinicalTrials.gov, CRIS)]
+[TODO: Protocol version number and date]
+```
+
+---
+
+## 6. Data Collection and Management
+
+**Format**: TODO markers with guidance notes
+
+```
+[TODO: List variables to be collected -- use your institution's CRF template]
+[TODO: Data collection method (chart review / prospective forms / electronic extraction)]
+[TODO: Data storage and security measures (encrypted database, access controls)]
+[TODO: Quality assurance procedures (double data entry, range checks)]
+[TODO: Data retention period per institutional policy]
+```
+
+---
+
+## 7. Ethical Considerations
+
+**Format**: TODO markers with jurisdiction-specific guidance
+
+```
+[TODO: IRB/Ethics committee name and expected submission date]
+[TODO: Informed consent process -- or justification for waiver]
+[TODO: Patient privacy and data protection measures]
+[TODO: Confirm applicable regulations with your IRB office]
+```
+
+Jurisdiction guidance:
+- Korea: PIPA, Bioethics and Safety Act
+- United States: HIPAA, Common Rule (45 CFR 46)
+- European Union: GDPR Article 9, Clinical Trials Regulation (EU 536/2014)
+
+See `ethics_checklist.md` for the full checklist.
+
+---
+
+## 8. Timeline and Milestones
+
+**Format**: TODO table
+
+```
+[TODO: Adapt to your project schedule]
+
+| Phase | Activity                              | Duration    | Target Date |
+|-------|---------------------------------------|-------------|-------------|
+| 1     | IRB approval                          | [X] weeks   | [TODO]      |
+| 2     | Data collection / Patient enrollment  | [X] months  | [TODO]      |
+| 3     | Data cleaning and analysis            | [X] months  | [TODO]      |
+| 4     | Manuscript preparation                | [X] months  | [TODO]      |
+| 5     | Submission                            | --          | [TODO]      |
+```
+
+---
+
+## 9. Budget
+
+**Format**: TODO markers with common categories
+
+```
+[TODO: Use your institution's budget template]
+
+Common cost categories (delete or add as needed):
+- Personnel (research coordinator, statistician)
+- Equipment and supplies
+- Software licenses
+- Statistical consultation
+- Publication fees (open access APC)
+- Patient compensation (if applicable)
+```
+
+---
+
+## 10. References
+
+**Format**: Numbered list, every entry with DOI or PMID
+
+```
+1. [Author] et al. [Title]. [Journal]. [Year];[Vol]:[Pages]. DOI: [DOI]
+2. [Author] et al. [Title]. [Journal]. [Year];[Vol]:[Pages]. PMID: [PMID]
+...
+```
+
+References are generated from:
+- Section 1 (Background and Rationale) citations
+- Section 3 (Sample Size Justification) effect size sources
+- Any additional references from cross-skill outputs
+
+Mark unverified references as: `[UNVERIFIED - NEEDS MANUAL CHECK]`

package/skills/write-protocol/skill.yml

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+schema_version: 2
+name: write-protocol
+layer: C
+owner_domain: protocol_drafting
+
+when_to_use: "Generate an IRB/ethics research protocol: 4 full prose core sections (Background, Design, Sample Size, Statistical Plan) plus 6 skeleton sections with TODO markers."
+when_NOT_to_use: "Filling an institutional Word form (use fill-protocol); manuscript drafting (use write-paper)."
+
+inputs:
+  - "design-study output"
+  - "calc-sample-size output"
+  - "search-lit output"
+outputs:
+  - "protocol.md (4 core sections + 6 TODO skeletons)"
+side_effects:
+  - writes_project_artifacts
+downstream_consumers:
+  - fill-protocol
+forbidden_actions:
+  - generate_references_from_memory
+  - fill_institution_specific_sections_with_invented_content
+
+# v2.1 quality card
+purpose: "Draft the scientific core of an IRB protocol and leave institution-specific sections as explicit TODO skeletons."
+safety_boundaries:
+  - "Institution-specific content is left as TODO markers, never fabricated."
+  - "Citations come from search-lit; references are not generated from memory."
+known_limitations:
+  - "Core sections need design-study/calc-sample-size inputs to be sound."
+  - "Skeleton sections require the researcher's institutional knowledge to complete."
+validation_commands:
+  - "/verify-refs --strict on cited work"
+  - "hand off to fill-protocol for the institutional template"
+evidence_surface: manual_workflow