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

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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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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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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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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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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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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)

http://www2.publicationsduquebec.gouv.qc.ca/dynamicSearch/telecharge.php?type=2&file=/A_2_1/A2_1_A.html

http://www2.publicationsduquebec.gouv.qc.ca/dynamicSearch/telecharge.php?type=2&file=/A_2_1/A2_1_A.html

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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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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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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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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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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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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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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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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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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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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

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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

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