REQAP & C.A.R.E welcomes you to the “Clinical Trials” series

1. REQAP & C.A.R.E welcomes you to the “Clinical Trials” series Part 1 Best practices for Negotiating Clinical Trial Agreements

2. Clinical Trials Series • PART 1: Best practices for negotiating Clinical Trial Agreements • PART 2: Diagnostic Medicine in the Research Context • September 8, 2009 • Francine & Charles Larente Nursing Lecture Hall (A-139) • 1:30-2:30pm • PART 3: How to Budget in the Research Context • December 1, 2009 • Francine & Charles Larente Nursing Lecture Hall (A-139) • 1:30-2:30pm

3. Clinical Trials Series – Best practices for Negotiating Clinical Trial Agreements • Goal: To provide information and knowledge to those involved in negotiating CTAs - Investigators and Research Coordinators How? Principles to be considered when negotiating a clinical trial agreement.

4. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements • Superior Principles • Volunteers are offering themselves for human experimentation. Hence, their safety must not only be, but must be seen to be, the overriding principle of the contract. • Ensure all applicable federal and provincial law and international regulations have as their purpose to protect the well-being of study participants. • Study participants are drawn from the general public and have submitted themselves to experiment in good faith. • The trial should be registered in public registry in order to permit publications.

5. Clinical Trials Series – Best practices for Negotiating Clinical Trial Agreements-Clinical Trial Agreement/Clinical Study Agreement • First page: Parties to the Contract Between: 1) Sponsor, a corporation ……adresss… 2) Lady Davis Institute of Medical Research of the Sir Mortimer B. Davis Jewish General Hospital (Institution) 3) Principal Investigator, an individual practicing at the Institution • Study name & Definitions Example: Investigator, Research Staff, Sub-Investigator, Obligations, Adverse events…

6. Clinical Trials Series Best Practice for Negotiating Clinical Trial Agreements Confidentiality

7. Clinical Trials Series – Best practices for Negotiating Clinical Trial Agreements-Clinical Trial Agreement/Clinical Study Agreement Confidential information usually includes: • Protocol • Investigator Brochures • Study Data • Biological Samples Analysis Data (Not the sample itself) • Any information provided to the investigator by the sponsor either in writing or orally

8. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality • Nature of confidentiality obligation: • Recipient of confidential information to maintain information in confidence using the same degree of care as recipient uses with its own confidential information and not less than a reasonable standard of care. • Access of restricted information by personnel with need to know. • Access of restricted information by the Institution’s/investigator’s staff with a need to know including the Institution’s Research Ethics Committee.

9. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality • Exclusions-Confidential Information does not usually include information that: • is already generally available to the public; • is publicly available information (including through publication is in accordance with terms of the study agreement) except through breach of the study agreement by the institution or investigator; • can be demonstrated to have been in the Institution’s or Investigator’s possession prior to the time of disclosure by Sponsor, and was not acquired directly or indirectly from Sponsor under an obligation of confidentiality;

10. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality • Exclusions-Confidential Information does not usually include information that-con’t: • becomes available to the Institution or Investigator from a third party which is not legally prohibited from disclosing such information, provided such information was not acquired directly or indirectly from Sponsor under an obligation of confidentiality; • the information can be documented to have been independently developed by Institution personnel who did not have access to Sponsor’s information.

11. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality • Permitted disclosures of confidential information – Confidential Information may be disclosed by Institution or Investigator: • When required to be disclosed by law, regulation, legal process; • To potential research participants during the recruitment process or to study subjects who are or were enrolled in the study, or their legal representatives, in order to obtain and maintain informed consent or as the information relates to their health, safety or diagnosis; • when otherwise permitted by agreement • When ethically required to be disclosed to patients because of any unforeseen risk identifies by either party during or after completion of the study

12. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality • Term of obligation of confidentiality: • Obligation survives termination/expiration of agreement but must have an end date, which is expected to be no more than 10 years; • If Institution/Investigator is required to return all confidential information to sponsor on termination of agreement, Institution/investigator may retain a copy if: • Required by law, regulation or in accordance with the provisions of ICH Good Clinical Practices or Health Canada Guidelines • Necessary to exercise site publication rights • For legal record keeping purposes

13. Clinical Trials Series Best Practice for Negotiating Clinical Trial Agreements Privacy

14. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Privacy • All parties agree to comply with applicable privacy legislations, specifically with the protection of confidential information. • Act respecting access to documents held by public bodies and the protection of personal informationby the Ministry of Health and Social Services of Quebec; • Loi sur l’accès aux documents des organisms publics et sur la protection des rensignements personnels (L.R.Q., c.A-2.1) (Quebec privacy Law) • PEPIDA (Canadian privacy law) • HIPPA (American Federal Law-must be removed)

15. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Privacy • No disclosure by recipient except in accordance with consent or as required by law; • This means in the course of performing the study, institution and PI process personal identifiable information only for the purpose of the study and will not allow any personal identifiable information to leave the institution • Also applicable to study subject’s biological samples & materials; • Sponsor’s right to access records for monitoring/auditing does not entitle them to copy items or documentation from the participants medical file.

16. Clinical Trials Series Best Practice for Negotiating Clinical Trial Agreements Indemnification Insure against loss: to provide somebody with protection, especially financial protection, against possible loss, damage, or liability Reimburse after loss: to pay compensation to somebody for loss, damage, or liability incurred

17. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification • Indemnities • A party including its/his/her trustees, directors, officers, affiliates, employees, agents, appointees (including Investigator and sub-Investigators), students, sub-contractors (if applicable), each being a separate indemnitee • The Sponsor is equally responsible for compensating the Investigator, his/hers employees and any person under his/her supervision. • Indemnitor has obligation to indemnities to: • Indemnify and hold harmless

18. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification • How is a Sponsor responsible for indemnification during a clinical trial (In the extent the claims arise out of or are caused by): • Conduct of the study (anything required by protocol, including without limitation injury to study subjects arising from administration of : • Study Drug • Study Device • Study Placebos • Study comparators • Study Procedures

19. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification • How is a Sponsor responsible for indemnification during a clinical trial (In the extent the claims arise out of or are caused by) cont’d: • Sponsor’s negligence, error, omission or intentional wrongdoing; including without limitation breach of clinical trail agreement and/or failure to conduct study in accordance with applicable laws;

20. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification • Study Participant Reimbursement – Medical care of participants: • Without limitation • A person may not exclude or limit his liability for material injury caused to another through an intentional or gross fault; a gross fault is a fault which shows gross recklessness, gross carelessness or gross negligence (Art. 1474 of The Quebec Civil Code) • The Sponsor will reimburse the institution / investigator / subject, as appropriate, for medical expenses incurred to treat injuries or illnesses arising: • the use of drug/device/ material of the study • Study protocol procedures • The subject’s private insurance provider should not be responsible for payment • Subjects should not be excluded due to own negligence

21. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification • Insurance • Physicians will maintain membership in the CMPA (Canadian Medical Protective Association) or equivalent • Sponsor must have general liability, product liability and/or clinical trial insurance coverage • Institution must have general liability coverage (AQESSS) • For clinical trials, it is expected that there be a minimum coverage of $5M, per occurrence and in the aggregate

22. Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements • Disclosure of Existence of Contract & Use of Name: • Institution/investigator have rights to disclose in customary reports of research funding: • Existence of agreement • Name of parties • Global amount of funding provided (for annual financial report purposes) • Name of study or protocol • Sponsor has right to disclose • Existence of agreement • Global amount of funding provided • Name of study or protocol • Names of institution and investigator, except for endorsement purposes No party has a right to use another party’s name in any way that suggests advertising or an endorsement that other party, without that other party’s prior written permission.

23. Clinical Trials Series Best Practice for Negotiating Clinical Trial Agreements Parties’ Rights & Obligations

24. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations - Parties’ Rights & Obligations • Compliance with applicable laws, regulations and guidelines: • Adverse event reporting obligations and rights of Sponsor and Institution/Investigator to be set out. This includes, in the event that the sponsor fails to do so, right of Institution/Investigator to report: • SAEs • Data Safety Monitoring Boards • Study Participants or their lawful representatives • Participating centers • Research Ethics Boards/Committees • Warranty by sponsor of study drug/device that drug/device shall be free of defects, and the manufacture, packaging and labeling of study drug/device shall be in full compliance with any requirements and specifications of Health Canada, and with Good Manufacturing Practices.

25. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations - Parties’ Rights & Obligations • Conflict of study documents: • Protocol versus agreement • Agreement prevails • Prior confidentiality agreement • Study agreement supersedes • Force majeure: • If Included, applies to all parties

26. Clinical Trials Series Best Practice for Clinical Trials Agreement Negotiations Publication

27. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations -Publication • Naming of Authors: • If authorship is included in the contract, authors should be named in accordance with established authorship guidelines of the International Committee of Medical Journal Editors (ICMJE) • What can be published by Institution/Investigation: • Site results can be published by Institution/Investigator; sponsor may delete its confidential information not including data/results or study methods sufficient for the requirements of an academic journal • Access to all site-specific data will be provided to the site • Consideration should be given to providing access to aggregate multi-site data • Right to publish interim and negative results

28. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations -Publication • When can Institution/Investigator publish site results? • Following the occurrence of the first of the following: • After the publication of multi-site data, or • After the sponsor indicates it will not publish multi-site data, or • After completion or abandonment of study at all sites AND • A 12 month delay (after database lock); • Sponsor review of the manuscript, no more than 45 days; • If needed, sponsor delay of the manuscript for the purpose of filing proprietary protection, no more than 90 days.

29. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations -Publication • Right of sponsor to copy and distribute site publications: • Sponsor’s right is subject to: • Permission of publishing journal if required • Acknowledgement of authorship • No use of institution/investigator name for endorsement purposes • Right of institution/investigator to name sponsor in a site publication: • Right to name sponsor in accordance with customary scientific practice as set out in ICMJE guidelines.

30. Clinical Trials Series Best Practice for Clinical Trials Agreement Negotiations Intellectual Property

31. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Intellectual Property • Ownership of Data (permissible): • Owned by sponsor • Owned by Institution • Owned jointly by sponsor and Institution Medical records of the research participants belong to the institution and may not be copied

32. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Intellectual Property • Use of data by institution/investigator if owned by sponsor or jointly owned. May be used by institution/investigator for: • Performance of study • Publication • For internal: • Administration • Academic purposes • Research purposes • Study subject care/clinical purposes • Use of data by sponsor if owned by Institution: • May be used by sponsor for regulatory submissions; other uses require permission of institution.

33. Clinical Trials Series Best Practice for Clinical Trials Agreement Negotiations Intellectual Property: Inventions

34. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Intel. Property: Inventions • Ownership of Inventions: • Subject to negotiation on study-by-study basis; options include: • Sponsor ownership • Institution ownership • Joint ownership by sponsor and institution All cost associated to the protection of intellectual properties are assumed by the sponsor.

35. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Intel. Property: Inventions • Use of inventions by institution if inventions owned by sponsor: • Non-exclusive royalty-free perpetual license to be used by institution/investigator for non-commercial, internal: • Administration • Academic purposes • Research purposes • Study subject care/clinical purposes • Use of inventions by sponsor if owned by institution: • At discretion of institution to negotiate on commercially reasonable terms the use for commercial purposes

36. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Termination Conditions • Disapproval by REB • Study Completion • Immediate termination • Usually safety issues, enrollment completed etc.. • Termination upon Notice • Sponsor and the institution reserve the right to terminate the study, upon written notice to the other party, if such party materially breaches this agreement and fails to cure such breaches within 30 days of receipt of written notice.

37. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Applicable Law • This Agreement is governed by the laws of the Province of Quebec, without reference to its conflicts of laws, provisions and the federal laws of Canada apllicable thereine. All disputes arising under this agreement will be referred to the courts of the Province of Quebec.

38. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Language Clause • Il est convenu par le présent acte que les parties demandent que ce contrat et tout avis, consentement, autorisation, communication et approbation soient rédigés en langue anglaise. It is hereby agreed that all aprties specifically require that this Agreement and any notices, consent, authorizations, communications and approvals be drawn up in the English language.

39. Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations –Signature Page • Sponsor • Name /Title • Date • Sir Mortimer B. Davis Jewish General Hospital on behalf of the Lady Davis Institute of Medical Research, a part of the Sir Mortimer B. Davis Jewish General Hospital Dr. Stéphane Richard Interim Director of Research Gustavo Wendichansky Research Grants and Awards Financial Officer\ • Qualified Investigator

40. REQAP & C.A.R.E “Clinical Trials” series Questions… Comments…

41. REQAP & C.A.R.E “Clinical Trials” series • Series To be Continued…. • “Diagnostic Medicine in the research context” to be held on September 8, 2009 at 1:30pm…