casemark/investigator-agreement

Investigator Agreement

Drafts a legally enforceable agreement governing the sponsor–principal investigator relationship for FDA-regulated clinical research.

Prerequisites

Gather before drafting:

1. Protocol — number, version, phase, design, investigational product, indication, enrollment target, endpoints, special populations
2. Parties — sponsor type (pharma/biotech/device/academic/government), CRO if any, PI credentials, institution legal name and type, governing state
3. Contracting structure — PI individually, institution as primary with PI signatory, or joint
4. Site personnel — sub-investigators, coordinators, specialists
5. Prior agreements/templates — mandatory provisions, indemnification policies, payment processing
6. Budget — per-subject, per-procedure, or hybrid; fair market value basis
7. Single-site vs. multi-center — affects publication rights, data ownership, oversight

Quick Start

1. Collect all prerequisites above
2. Draft each section below, adapting to institutional type and study specifics
3. Replace all bracketed [X] placeholders with client-specific values
4. Run through the Drafting Checks at the end
5. For detailed regulatory tables and reference material, see references/REGULATORY.md

Agreement Sections

1. Recitals & Definitions

• Full legal names and roles for all parties
• Define: Protocol, Investigational Product, Study Site, Confidential Information, Study Data, Serious Adverse Event, Effective Date, Study Completion

2. Investigator Obligations

Key regulatory obligations to address:

| Obligation | Regulatory Basis | Core Requirement | |---|---|---| | Protocol compliance | 21 CFR 312.60 / 812.110 | Absolute; deviations only for immediate hazard; report within 24 hrs | | Delegation | ICH E6(R2) §4.2 | Signed delegation log; PI retains ultimate responsibility | | IP accountability | 21 CFR 312.62 / 812.140 | Receipt, storage, dispensing, return/destruction records | | Informed consent | 21 CFR 50; ICH E6(R2) §4.8 | Written consent before any study procedure; current IRB-approved form | | Vulnerable populations | 45 CFR 46 Subparts B/C/D | Additional protections; immediate notification for status changes | | HIPAA | 45 CFR 164 | PHI authorization; coded CRF identifiers; breach reporting |

3. IRB Governance

• Initial submission: Complete package before any subject contact
• Continuing review: Per IRB schedule with enrollment counts, AE summary, deviations
• Amendments: IRB + sponsor approval before implementation; exception for immediate hazard (document, notify within 24 hrs)
• Reporting: SAEs (unexpected + possibly related), unanticipated problems, deviations increasing risk
• Lapse: Cease all activities; exception for enrolled subject safety monitoring
• Document flow: IRB submissions/correspondence to sponsor within 5 business days

4. Data Integrity & Documentation

• Apply ALCOA+ principles (Attributable, Legible, Contemporaneous, Original, Accurate + Available, Consistent, Enduring, Traceable)
• All CRF entries verifiable against source documents
• Corrections: single line-through (paper) or audit trail (EDC); date, initial, reason
• Essential documents per ICH E6(R2) §8 — FDA 1572, financial disclosures, IRB correspondence, signed ICFs, delegation log, IP records, protocol versions, lab certifications
• Retention: longest of — 2 years post-marketing approval (or 2 years post-discontinuation + FDA notification), institutional policy, or state law; notify sponsor before destruction

5. Adverse Event Reporting

| Category | Timeline | Recipient | |---|---|---| | All AEs | Document regardless of severity/causality | Study file | | SAEs | Within 24 hours of awareness | Sponsor | | Unanticipated problems involving risk | Per IRB policy | IRB | | Sponsor safety reports | Review + submit per IRB policy | IRB |

6. Monitoring & Inspection

• Sponsor monitoring: Business hours; ≥1 week notice (except urgent); direct source document access; PI responds promptly to findings
• Regulatory inspections: Notify sponsor within 24 hours of FDA/authority contact; cooperate fully; provide copies of FDA 483, EIR, warning letters within 5 business days
• Corrective actions: Collaborative development with sponsor; document implementation

7. Confidentiality & IP

• Scope: Protocol, IB, CRFs, study data, product formulation, regulatory strategy, all non-public sponsor information
• Duration: Study term + [3–5] years post-termination or until publicly available
• Permitted disclosures: IRB, regulators, study personnel (bound by equivalent obligations), legal counsel
• Return/destruction: Upon request or termination; retain one regulatory copy; certify electronic deletion
• Data ownership: Sponsor owns all data, results, discoveries, inventions; survives termination
• Biological samples: Sponsor-owned; subject to institutional policies on genetic testing/destruction

8. Publication Rights

• Eligible after study completion + database lock + primary analyses
• Review period: Submit to sponsor [45–60] days before submission/presentation
• Sponsor rights: Remove confidential information; delay [60–90] days for patent filing; request accuracy modifications
• Anti-suppression: Sponsor may not suppress legitimate scientific findings; independent expert dispute resolution
• Authorship: Per ICMJE guidelines

9. Financial Terms

• Compensation: Per-subject/per-procedure/hybrid; attach itemized budget as exhibit
• Fair market value: Based on time, effort, complexity, qualifications, local rates; Anti-Kickback Statute compliant
• Invoicing: [Monthly/quarterly]; payment within [30–45] days of compliant invoice
• Adjustments: Screen failures at [specified rate]; early withdrawals pro rata; no payment for unusable data from PI non-compliance
• Reimbursable costs: Protocol-required labs/imaging, pharmacy fees, IP storage, subject stipends/travel; pre-approval above [threshold]
• Financial disclosure: Per 21 CFR 54 — equity >$50K, prior-year compensation >$25K (excluding study payments), proprietary interests; update during study

10. Indemnification & Insurance

Sponsor indemnifies for: protocol design, IP formulation/manufacture/defects, product-related injuries when used per protocol.

Exceptions: PI negligence/willful misconduct, failure to follow informed consent, unauthorized deviations, agreement breach, regulatory non-compliance.

Insurance minimums:

| Party | Per Occurrence | Aggregate | |---|---|---| | Sponsor (clinical trial liability) | $[1–5]M | $[2–10]M | | PI/Institution (professional liability) | $[1–3]M | $[3–5]M |

• Certificates of insurance required; 10-day claims notice; indemnifying party controls defense
• Academic/public institutions typically cannot indemnify — rely on professional liability insurance with specified minimums instead

11. Term & Termination

| Trigger | Notice | Effect | |---|---|---| | Study completion | N/A | Ends after closeout complete | | Sponsor convenience | [30–60] days written | Payment through termination + wind-down costs | | Sponsor for cause | Immediate | May seek damages; may report to FDA/ORI | | PI — sponsor breach | 30-day cure period | Effective after cure period | | PI — sponsor insurance lapse | Written notice | Effective upon notice |

Wind-down: PI ceases enrollment, notifies subjects, completes CRFs, returns IP/confidential info, submits final IRB report. Sponsor pays for completed services and reasonable wind-down costs.

12. Governing Law & Disputes

• Governing law: [Sponsor's state] for contract; site jurisdiction for research conduct/malpractice
• Escalation: project managers → institutional/sponsor executives → mediation (shared costs) → litigation
• Consider arbitration based on party preferences

13. Representations & Warranties

• Sponsor: Authority to contract; effective IND/IDE; IB contains all known safety information; will maintain insurance; IP manufactured per regulations
• PI: Authority to contract; qualified and licensed; disclosed all financial interests; adequate facilities/personnel; not debarred from clinical research
• Disclaimer: No implied warranties; investigational product is experimental

14. Compliance Provisions

• Anti-corruption: FCPA/UK Bribery Act; if PI is government official, institutional compliance review; immediate termination for violation
• Export controls/sanctions: PI not on OFAC/SDN lists; no export of IP to restricted parties
• Healthcare compliance: Anti-Kickback Statute, False Claims Act, Sunshine Act; compensation = FMV

15. Execution & Exhibits

• Signature blocks: Authorized institutional official (not just PI) for institutional agreements; PI signature for personal obligations
• Startup timeline: Allow [6–12] weeks for institutional review
• Exhibits: A: Protocol, B: Budget, C: Personnel List, D: PI CV, E: Financial Disclosures, F: Institutional Policies
• Amendments: Material changes require written amendment signed by both parties

Drafting Checks

• [ ] All [X] placeholders replaced with client-specific values
• [ ] Contracting structure and indemnification adapted to institutional type (academic centers typically cannot indemnify)
• [ ] For device studies, 21 CFR 812 substituted for Part 312 references throughout
• [ ] Publication terms include ICMJE-compliant authorship and anti-suppression language
• [ ] Financial terms withstand fair market value scrutiny under Anti-Kickback Statute
• [ ] Multi-center provisions address publication timing and data consistency coordination
• [ ] State-specific requirements checked (informed consent, medical records retention)
• [ ] All regulatory citations verified against current CFR versions