Transcript Document 7880950

REQAP & C.A.R.E
welcomes you to the
“Clinical Trials” series
Part 1
Best practices for Negotiating Clinical
Trial Agreements
1
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 Principles
1.
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 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…
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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 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
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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.
ii.
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:
o the use of drug/device/ material of the study
o Study protocol procedures
The subject’s private insurance provider should not be responsible for
payment
Subjects should not be excluded due to own negligence
iii.
iv.
v.
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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
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
2.
3.
4.
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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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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:
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.
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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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REQAP & C.A.R.E
“Clinical Trials” series
Questions…
Comments…
40
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…
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