Youve Successfully Negotiated Those Darned Terms and Conditions' The Contract is Signed and The Saga

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Youve Successfully Negotiated Those Darned
Terms and Conditions. The Contract is Signed and
The Saga Begins

• Ronald F. Polizzi, MBA, CRA
• Associate Director, Contracts
• Lee G. McDaid, MS
• Associate Director, Research Services

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Goals and Objectives

• Pesky Provisions
• Challenging Clauses
• Compliance, Compliance, Compliance!
• Questions

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Clinical Trial Contract A Discussion of Four
Selected Provisions

• Publication, Intellectual Property,
  Indemnification, Subject Injury
• Available at
• www.aamc.org/publications

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Contractual Terms

• Names of Parties/Signature
• Whereas (Recitals/Background)
• Conduct/Protocol/IRB Approval/Modification
• Sponsor Compliance/Adverse Events
• HIPAA
• Payment
• Publication
• Confidentiality
• Data
• Intellectual Property
• Indemnification
• Insurance
• Subject Injury
• Termination
• Other terms

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Parties/Signature/Recitals

• Names of Parties/Signature
• Does the contract correctly name Parties?
• Address
• Other Sites?
• PI/Employee or not?
• Read Agreed/Acknowledged/Understood
• Whereas/Recitals/Background
• Subject Matter
• Sponsor Description
• Institution Purpose

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Conduct/Protocol/IRB Approval/Modification

• Sponsor provides Institution with Protocol
• Work shall not begin without IRB approval
• Informed Consent
• Sponsor may modify protocol with IRB approval
  provide option to terminate
• Protocol Deviation
• Protocol Conflict with Contract

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Institution Compliance

• Comply with all legal and regulatory requirements
• PI will adhere to conditions imposed by the local
  IRB
• FDA, CFRs, DEA, GCPs
• ICH, Declaration of Helsinki, Nuremberg Code
• HIPAA
• Monitoring

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Sponsor Compliance

• Patient Safety/Drug Safety
• Request Sponsor to assume responsibility for
  their own legal compliance
• Choosing qualified PI
• Providing PI with information required to adhere
  to protocol
• Maintain IND report adverse events to PI
• HIPAA

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Payment

• Performance of study/financial support
• Up front payment - one subject
• Prorate not large at study end
• Do not accept terms
• Tied to successful outcomes
• Enrollment numbers
• Finder fees
• Fixed fees
• Non refundable up front for study preparation
• IRB Annual Fees
• Institution overhead rate

10
Publication

• The Academic institution cannot accept language
  that restricts publications
• Fulfill mission no editorial rights
• Disseminate fruits of research without bias,
  irrespective of funding source 
• Methods, data, results
• Sponsor prevent unfavorable or neutral results
• Delay Not to exceed 90 days - review, comment,
  delay for patent protection
• Multi center delay not to exceed 12 months
• Trial completion or database lock

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Confidentiality

• Define confidential information
• Inclusion/exclusion
• Information must be identified in writing
• If verbal, reduce to writing (15 days)
• Endeavor to mark
• Right to refuse
• Not designate non confidentiality if apparent
• Copy for non-commercial, educational purposes
• Ensure a reasonable time period (3, 5, 7 years)
• Third party disclosure

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Data

• Sponsor owns case report forms (CRFs)
• Sponsor owns Other protocol required reports,
  drugs, supplies, devices
• Institution owns original records including
  medical record and lab notebooks
• Institution retains right to use data for its
  internal research and academic purposes

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Intellectual Property

• Sponsor ownership direct performance
• Sponsors protocol
• Sponsors expense
• Non-exclusive, non-transferable, royalty-free
  license for internal research and educational
  purposes
• Institution ownership Outside the protocol
  scope
• File patent
• Provide sponsor 6 month opportunity to negotiate
  license

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Indemnification

• Sponsor wants prompt notice, full cooperation
• Negligence (failure to follow protocol), willful
  misconduct
• Permit sponsor to defend
• Applicable laws, regulations
• Institution wants defend, indemnify, hold
  harmless
• All liabilities, demands, damages, expenses,
  loss, including
• Claims resulting from protocol performance
• Results or use of data, publication
• Dont indemnify sponsor if possible

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Insurance

• Sponsor will maintain adequate insurance coverage
• Insurance limits set according to risk
• Institution must have insurance for its
  indemnification issues
• Silent

16
Subject Injury

• Informed Consent must match contract.
• Sponsor responsible for injuries resulting from
  patients participation in the study
• Institution will accept third party billing
• No underlying illness, negligence, deviation
  subject not adhering to instructions

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Termination

• Either party may terminate
• Emergence of safety issue
• Sponsor to pay pro rata or non-cancelable
  obligations
• Breach
• Replacement of Investigator

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Non-Commercial Terminology Use Dont Use

• Clinical Research Agreement
• Study
• Research
• Institution, University, Non-Profit, Organization
• Funding, Support, Grant

• Clinical Trial Agreement
• Trial
• Services
• Contractor, Vendor, Provider, Business Associate
• Payment

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Other Terms

• Use of Name
• Names, symbols, marks, logotypes
• Limited to identification of site/staff
• Permit to use in fed grant applications
• Integration
• Representation (fact) / Warranty (guarantee)
• Research As is
• Avoidable Phrases
• Best Efforts
• satisfactory acceptance, to the satisfaction, or
  upon satisfactory completion
• Time is of the essence

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Compliance
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Compliance Issues

• Informed consent
• Billing
• Anti-kickback Statute
• HIPAA
• False Claims Act
• Conflict of Interest
• Data management/Record Retention/Ownership
• Adverse Events
• IND requirements
• Leftover study drugs
• Patient safety

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Informed Consent

• A process, not just a form

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Informed Consent (45CFR46.1160)

• Insurance that no human subject will be involved
  in the research prior to obtaining consent
• Responsibility for insuring that informed consent
  is documented by using the IRB-approved form
• Responsibility for retention of signed consent
  documents in the study file in a safe place

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Informed Consent (45CFR46.1160)

• Procedures used in obtaining informed consent
  should be designed to educate the subject
  population
• Consent must be obtained from the subject or the
  subjects legally authorized representative
• Consenting process must identify contact persons
  who are knowledgeable in the areas of the
  research, the rights of the research subjects,
  and research-related injuries

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Adverse Events (DHHS 45CFR46, FDA 21CFR56)

• On-Site AEs
• Unanticipated AEs must be reported to the IRB
  within 48 hrs.
• Fatal AEs which are unanticipated must be
  reported with 24 hrs.
• Fatalities not related to the study drug/device
  must be reported within 5 days

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Adverse Events (DHHS 45CFR46, FDA 21CFR56)

• Off-site AEs that are serious and unanticipated
• Subject to review by the PI, the sponsor and the
  FDA
• Data Safety Monitoring Board large multi-center
  clinical trial
• If directly related to the study drug and
  requires a change to the protocol, the PI must
  inform the IRB within 5 days

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Conflict of Interest (45CFR46.107(d))

• Belmont principles of respect for persons,
  beneficence, and justice should not be
  compromised by financial relationships
• Concerns center around financial relationships
  and financial interest may affect the rights and
  welfare of human subjects
• Conflicts need to be reduced, managed or
  eliminated

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Billing

• Increasingly complex
• Diversity of coverage and payment rules
• Volume of claims
• Billing systems generally not designed at the
  outset
• Mix of services
• Standard of care
• research-related services
• Need for serious delineation
• Billing errors
• double dipping
• Billing the insurance for trial services
• Residual balances
• Policies should be developed to address balances

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False Claims Act

• Qui tam suits
• Knowing submissions
• The institution has actual knowledge of the
  false/fraudulent claim
• The institution deliberately ignored the
  falsity of the claim
• The institution recklessly disregarded the
  truth or falsity of the claim

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HIPAA

• Protection the security and privacy of health
  information and to improve the efficiency and
  effectiveness of the electronic transmission of
  healthcare information, including standards for
• Healthcare transactions
• Unique identifiers for individuals, employees,
  health providers and health plans
• Security of healthcare information
• Electronic signatures

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HIPAA

• Research requiring special consideration of
  subject privacy and confidentiality
• Chart reviews requiring the ability to obtain
  follow-up data
• Use of tissue or other biological specimens
• Genetic analysis on specimens from research
  subjects
• Genetic material to be transferred to a research
  subject
• AIDS/HIV research

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Investigational Drugs(http//www.fda.gov/oc/gcp/r
egulations.html)

• Assurance of return of all unused drugs once the
  study in concluded/terminated
• Controlled substances
• Storage of the IND
• Prevention of theft/diversion
• Prevention of any unauthorized individual from
  receiving the drug
• Administer only to subjects under the
  investigators personal supervision and/or
  sub-investigator

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IDE (Investigational Devices) Requirements
(21CFR812.36)

• The investigation must be conducted in accordance
  with the signed agreement with the sponsor, the
  investigational plan, and applicable FDA
  regulations
• An investigator shall permit an investigational
  device to be used only with subjects under the
  investigator's supervision. An investigator shall
  not supply an investigational device to any
  person not authorized under this part to receive
  it.
• An investigator shall return to the sponsor any
  remaining supply of the device or otherwise
  dispose of the device as the sponsor directs.

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General Considerations

• Planning
• Training and Education
• Coordination
• Accountability
• Documentation, documentation, documentation

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Questions?

• Ron Polizzi
• Ronald.Polizzi_at_jefferson.edu
• 215-503-2127
• Lee McDaid
• Lee.McDaid_at_jefferson.edu
• 215-503-2890