Create a risk-benefit analysis attachment for the IRB Application covering pediatric biobank specimen use in CRISPR-gene-editing rheumatology studies

Study Protocol & Supporting Documents *

Pediatric Age Subgroup * Select age category Neonates (0-27 days) Infants (28 days-23 months) Toddlers/Preschool (2-5 years) School age (6-11 years) Adolescents (12-17 years) Mixed age groups across categories Emancipated minors

CRISPR Technique & Vector Details * Choose technique and delivery method Ex vivo CRISPR-Cas9 with lentiviral delivery In vivo AAV-mediated CRISPR delivery Ex vivo electroporation with CRISPR ribonucleoprotein complexes In vivo lipid nanoparticle (LNP) delivery CRISPR base editors without double-strand breaks Prime editing systems Multiple CRISPR modalities combined

Biobank Specimen Type & Volume * Choose specimen type Whole blood (≤1 mL) Peripheral blood mononuclear cells (PBMCs) Bone marrow aspirate Synovial fluid Skin/soft tissue biopsy Cartilage biopsy Induced pluripotent stem cells (iPSCs) Archived DNA/RNA samples only Multiple specimen types combined

Regulatory Framework Context * Choose regulatory framework FDA IND-approved phase I/II trials NIH RAC-approved protocol Registry of Novel Application (RoNA) submission Expanded access/compassionate use International collaborative study (non-US sites) Subpart D pediatric research exemption HIPAA de-identified specimen use Single IRB (sIRB) reliance agreement State-specific pediatric gene therapy regulations

Risk-Benefit Assessment Level * Choose assessment level Preclinical safety data summary comparison Target organ toxicity assessment Off-target effects analysis with dual-guide validation Long-term follow-up (LTFU) protocol design Age-appropriate consent/assent considerations Genetic counseling implications Healthcare resource utilization analysis Quality-adjusted life years (QALY) modeling Comparative effectiveness vs standard care

Stakeholder Review Requirements * Choose review bodies Pediatric IRB subcommittee complete review Data Safety Monitoring Board (DSMB) review Clinical Ethics Committee consultation Institutional Biosafety Committee (IBC) approval Conflict of Interest Committee clearance Pediatric Advisory Board input Patient/Parent Advisory Panel review Community member consultation External pediatric CRISPR expert consultation

Therapeutic Target & Disease Impact *

Follow-up Duration & Monitoring * Choose monitoring period 15-year follow-up (FDA gene therapy minimum) Life-long registry participation Gene-specific variant monitoring Germline transmission risk assessment Reproductive health surveillance Developmental milestone tracking Multi-generational family cohort monitoring International pediatric CRISPR outcomes database

Ethical Considerations & Mitigation *

Output Format & Detail Specifications * Select output requirement Full IRB protocol appendix with executive summary Detailed FDA IND safety report Pediatric Investigational Plan (PIP) chapter Institutional biosafety file documentation DSMB charter with monitoring plan Parent-friendly risk communication summary Regulatory evidence package for international trial Risk-evaluation and mitigation strategies (REMS) document