1. Legal Aspects of Clinical Trials Shekhar Potkar Director Clinical Research Pfizer Limited

2. Why is law necessary in clinical research?

3. Jesse Gelsinger vs University of Penn OTC deficiency OTC deficiency Gene therapy experiment with Adenovirus vector Gene therapy experiment with Adenovirus vector No direct benefit, minimal risks, benefit to others No direct benefit, minimal risks, benefit to others Conducted by Dr Wilson, IHGT at University of Penn sponsored by Genovo Conducted by Dr Wilson, IHGT at University of Penn sponsored by Genovo Died of jaundice, kidney failure, lung failure, brain death Died of jaundice, kidney failure, lung failure, brain death Alan Milstein sued the University, Dr Wilson and Genovo Alan Milstein sued the University, Dr Wilson and Genovo Risks not explained, negligence, conflicts of interests of Dr Wilson with Genovo Risks not explained, negligence, conflicts of interests of Dr Wilson with Genovo ~ 10 million in settlement ~ 10 million in settlement

4. Why Law in Clinical Research? Risk management perspective Risk management perspective Stakeholders interests perspective Stakeholders interests perspective

5. Agenda Legal agreements Legal agreements Legal implications Legal implications

6. Agreements

7. Elements of a Contract Parties Parties Offer Offer Consideration Consideration Acceptance Acceptance Remedy Remedy

8. Major Agreements Non Disclosure Agreement Non Disclosure Agreement Investigator undertaking/agreement Investigator undertaking/agreement Clinical trial agreement Clinical trial agreement Indemnity and insurance Indemnity and insurance Services contract Services contract

9. Non Disclosure Agreement PI and Sponsor PI and Sponsor Protection of proprietary information Protection of proprietary information Binding on site staff Binding on site staff Site responsibility Site responsibility

10. Investigator Agreement Undertaking by a PI to the regulatory agency Undertaking by a PI to the regulatory agency Compliance to GCP and applicable laws Compliance to GCP and applicable laws Legal sanctions in case of violations Legal sanctions in case of violations

11. Clinical Trial Agreement Bipartite or tripartite Bipartite or tripartite Nature of work – responsibilities and compliance Nature of work – responsibilities and compliance Consideration Consideration Milestones Milestones Issue resolution Issue resolution Publication Publication –Right to publish –Data access –Opportunity to review –Multi center studies Intellectual property Intellectual property –Sponsor –Data protection Trial related injury Trial related injury

12. Indemnity/Insurance Indemnity Indemnity –Investigator, other staff and institute –Exceptions -Noncompliance/ Misconduct/ negligence –Role of a CRO Clinical trial insurance Clinical trial insurance

13. Services Agreement CROs, Labs, SMOs Bipartite Bipartite Nature of services e.g. monitoring, lab analysis, site management Nature of services e.g. monitoring, lab analysis, site management Terms Terms Consideration Consideration Remedies Remedies

14. Legal Implications

15. Informed consent Autonomy Autonomy Valid consent – informed, competent (capacity), voluntary Valid consent – informed, competent (capacity), voluntary Competence - Understanding, reasoning, values Competence - Understanding, reasoning, values Incompetence - Best interests, proxy, substituted judgement, advance directives Incompetence - Best interests, proxy, substituted judgement, advance directives Consent form as mechanism and evidence Consent form as mechanism and evidence Battery versus Negligence - e.g. partial colectomy Battery versus Negligence - e.g. partial colectomy

16. Confidentiality Fiduciary role Fiduciary role –Patient autonomy –Implied promise –Virtue ethics –Consequentialism Balancing of public interests Balancing of public interests HIPAA – covered entities should use PHI for TPO only, consent necessary for any other use HIPAA – covered entities should use PHI for TPO only, consent necessary for any other use

17. Conflict of interests Therapeutic misconception Therapeutic misconception Financial conflicts Financial conflicts –Disclosure

18. Conclusions

19. Ethics and law for human subject protection Ethics and law for human subject protection Legal framework for commercial aspects for research Legal framework for commercial aspects for research

20. Role of Ethics committee Check risk management framework Check risk management framework –Informed consent process, –Patient confidentiality –Conflict of interest –Financial aspects including trial related injury –Publication policy