1 REQAP & C.A.R.E welcomes you to the “Clinical Trials” series Part 1 Best practices for...
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Transcript of 1 REQAP & C.A.R.E welcomes you to the “Clinical Trials” series Part 1 Best practices for...
1
REQAP & C.A.R.E welcomes you to the
“Clinical Trials” series
Part 1Best practices for Negotiating Clinical
Trial Agreements
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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
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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.
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements
Superior Principles1. 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.
2. Ensure all applicable federal and provincial law and international regulations have as their purpose to protect the well-being of study participants.
3. Study participants are drawn from the general public and have submitted themselves to experiment in good faith.
4. The trial should be registered in public registry in order to permit publications.
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Clinical Trials Series – Best practices for Negotiating Clinical Trial Agreements-Clinical Trial Agreement/Clinical Study
Agreement
First page:
Parties to the ContractBetween:
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 & DefinitionsExample:
Investigator, Research Staff, Sub-Investigator, Obligations, Adverse events…
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Clinical Trials Series
Best Practice for Negotiating Clinical Trial Agreements
Confidentiality
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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
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality
Nature of confidentiality obligation:
i. 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.
ii. Access of restricted information by personnel with need to know.
iii. Access of restricted information by the Institution’s/investigator’s staff with a need to know including the Institution’s Research Ethics Committee.
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality
Exclusions-Confidential Information does not usually include information that:
i. is already generally available to the public;
ii. 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;
iii. 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;
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Confidentiality
Exclusions-Confidential Information does not usually include information that-con’t:
iv. 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;
v. the information can be documented to have been independently developed by Institution personnel who did not have access to Sponsor’s information.
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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;i. 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;
ii. when otherwise permitted by agreement
iii. When ethically required to be disclosed to patients because of any unforeseen risk identifies by either party during or after completion of the study
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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:
i. Required by law, regulation or in accordance with the provisions of ICH Good Clinical Practices or Health Canada Guidelines
ii. Necessary to exercise site publication rights
iii. For legal record keeping purposes
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Clinical Trials Series
Best Practice for Negotiating Clinical Trial Agreements
Privacy
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Privacy
i. 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 information by 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)
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Privacy
i. No disclosure by recipient except in accordance with consent or as required by law; i. 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
ii. Also applicable to study subject’s biological samples & materials;
iii. Sponsor’s right to access records for monitoring/auditing does not entitle them to copy items or documentation from the participants medical file.
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Clinical Trials SeriesBest Practice for Negotiating
Clinical Trial Agreements
IndemnificationInsure against loss: to provide somebody with protection, especially
financial protection, against possible loss, damage, or liabilityReimburse after loss: to pay compensation to somebody for loss,
damage, or liability incurred
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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
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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 :
i. Study Drug
ii. Study Device
iii. Study Placebos
iv. Study comparators
v. Study Procedures
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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;
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification Study Participant Reimbursement – Medical care of
participants:i. Without limitationii. 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)
iii. The Sponsor will reimburse the institution / investigator / subject, as appropriate, for medical expenses incurred to treat injuries or illnesses arising:
o the use of drug/device/ material of the study o Study protocol procedures
iv. The subject’s private insurance provider should not be responsible for payment
v. Subjects should not be excluded due to own negligence
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Clinical Trials Series – Best Practice for Negotiating Clinical Trial Agreements - Indemnification
Insurance
1. Physicians will maintain membership in the CMPA (Canadian Medical Protective Association) or equivalent
2. Sponsor must have general liability, product liability and/or clinical trial insurance coverage
3. Institution must have general liability coverage (AQESSS)
4. For clinical trials, it is expected that there be a minimum coverage of $5M, per occurrence and in the aggregate
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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.
•
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Clinical Trials Series
Best Practice for Negotiating Clinical Trial Agreements
Parties’ Rights & Obligations
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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:
i. SAEs
ii. Data Safety Monitoring Boards
iii. Study Participants or their lawful representatives
iv. Participating centers
v. 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.
Clinical Trials Series – Best Practice for Clinical Trials Agreement Negotiations - Parties’ Rights & Obligations
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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
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Clinical Trials Series
Best Practice for Clinical Trials Agreement Negotiations
Publication
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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
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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
i. A 12 month delay (after database lock);
ii. Sponsor review of the manuscript, no more than 45 days;
iii. If needed, sponsor delay of the manuscript for the purpose of filing proprietary protection, no more than 90 days.
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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.
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Clinical Trials Series
Best Practice for Clinical Trials Agreement Negotiations
Intellectual Property
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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
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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:
i. Administration
ii. Academic purposes
iii. Research purposes
iv. 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.
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Clinical Trials Series
Best Practice for Clinical Trials Agreement Negotiations
Intellectual Property:
Inventions
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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:1. Sponsor ownership
2. Institution ownership
3. Joint ownership by sponsor and institution
All cost associated to the protection of intellectual properties are assumed by the sponsor.
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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:
1. Administration
2. Academic purposes
3. Research purposes
4. 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
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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.
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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.
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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.
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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
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Questions… Comments…
REQAP & C.A.R.E “Clinical Trials” series
41
Series To be Continued….• “Diagnostic Medicine in the research context” to be held on September 8, 2009 at 1:30pm…
REQAP & C.A.R.E “Clinical Trials” series