Contracting Clinical Trials

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THE CLINICAL RESEARCH CONTRACTING PROCESS 

What you should know about Clinical Research Contracts but never bother to ask00 

NEVER SIGN UNTIL REVIEWED

AND APPROVED  

Kenneth N. Geller, Ph.D.

Associate Vice Provost for Research/HSC

October 23, 2003

 
 
 

Overview 

      Definition of Terms

            Types of Research Contracts/Agreements

            Contract

            Contracting Parties

            Institutional Review Board (IRB)

            Federal Wide Assurance (FWA)

            Informed Consent 

      General & Special Contract Provisions

      The Contract Review Process

      Investigator Code of Conduct

 
 
 

Types of Clinical Research 

Investigator Initiated (your idea; know-how; study design)

Federal Agency (NIH, NSF, DOD, 00) Foundations (AHA, Susan B. Koman, Hughes, Corp,00.) Contract research (Big/Small Pharma/Med Device Co, 00

4. Collaborative research (another institution) 

Sponsor Initiated (their ideas; drug/device/biologic; protocol)

1. Clinical trials (Phase I, II, III, IV)

2. Contracted professional services

Consulting services - tests & evaluations  
 
 

The Research Contract 

A legally binding Agreement involving an: 

      - Offer (from Pharmaceutical/Medical Device Co - Sponsor)

      - Acceptance (by Institution & Investigator)

      - For services & results (by Institution & Investigator)

      - In exchange for money (from Sponsor to conduct the    research/trial) 

 
 
 

Clinical Research/Trial 

Any experiment or study in which one or more human subjects receives a drug, biologic, device or procedure for the purpose of determining its potential beneficial effects, and/or safety and efficacy for diagnostic, therapeutic, or preventative use.

 
 
 

Contracting Parties 
in Clinical Research 

Federal Government 
 FWA with DHHS (on file with OHRP) Subjects 
 Informed Consent Sponsor 
 Clinical Research/Trial Agreement  
 
 

Federalwide Assurance (FWA) 

Assures OHRP of Temple00 commitment to protect human research subjects and comply with Federal Policy for the Protection of Human Subjects  (the Common Rule) 00DHHS regulations 45 CFR Part 46. Sets forth the responsibilities of: Institution Institutional Official (Vice Provost for Research) Institutional Review Board (IRB) Research Investigator A signed 00greement00of Compliance / Assurance Temple00 Certification: FWA00004964  
 
 

Informed Consent 

Provide prospective subject or representative sufficient information to consider whether or not to participate in the research study. 

Requirements:

Full disclosure

         it00 research; what is being done; why it is being done

         potential risks/benefits; alternative treatment;

         confidentiality; compensation (if any);

         contact; subject injury

Comprehension (8th grade?) Voluntary Agreement

         signed by investigator & subject

 
 
 

Contracting CTR-Schematic Overview 

INSTITUTION

PI 

SPONSOR 

Protocol (study design) Study Drug/Device/Biologic Compensation ($$)  
Patients IRB Approval Results (CRFs) Intellectual Property Publications  

Responsibilities

of

Sponsor 

Responsibilities

of PI &

Institution 

FDA & OHRP (FWA) 

Human Subjects (Patient ICF)

 
 
 

Who are the SPONSORS? 

Pharmaceutical/Medical Device Companies Biotech Companies CROs (Contract Research Org) SMOs (Site Management Org) Consultants  
 
 

The Contract Structure 

General Provisions Special Provisions Miscellaneous Provisions Exhibits & Addenda  
 
 

General Provisions 

Scope of Work (Study Protocol) Personnel (Identify PI & Sub-investigators) Term (Enrollment period) Recordkeeping and Access (CRFs) Notice (Institution & Sponsor contacts) Assurances (IRB approval, ICF, HIPAA-AF) Independent Contractor (not part of Sponsor) Use of Name (when authorized) Completeness  
 
 

Special Provisions 

Cost and payment terms 
- incentives (enrollment & time targets)  
- administrative fees (dept & university overhead) 
- infrastructure costs (IRB, advertising, pharmacy) Confidential information HIPAA Compliance Publication rights Intellectual Property rights Indemnification of Institution & PI by Sponsor Subject Injury Insurance Financial Disclosure (effective 2/2/99) 
 
 
 

Miscellaneous Provisions 

Governing/Controlling law (PA) Ammendments & Severability Assignment Return of drugs Record retention for 0000 years Debarment warranty  
 
 

Exhibits/Amendments 

Itemized cost breakdown Schedule of payments Protocol 00by reference  
 
 

Financial Disclosure 
(Conflict of Interest) 

Used by FDA to determine whether the financial interests of those involved in the study have influenced the outcome of the study.  Financial interests or arrangements include:

          -  compensation for carrying out the study is affected by its    outcome 
 -  significant payments other than the cost of study (e.g. travel,    honoraria, equipment, research funding, etc. > $25,000/study) 
 -  proprietary interest in the study product (e.g. holder of patent) 
 -  significant equity interest (>$50,000 for 1 yr after study) 
 
FDA 3455 - completed by Investigator(s) 
FDA 3456 - completed by Sponsor

 
 
 

Confidentiality 

Obligates Institution, PI and sub-investigators to maintain sponsor information in confidence for 5-10 years. Does not apply to information that is:

      - in the public domain

      - known to Institution or PI before start of Study

      - disclosed by 3rd party with a right to do so

      - required by law to be disclosed

      - necessary to assure proper medical care

 
 
 

Publications - Guiding Principle 

ICMJE (Sept. 2001) 00Uniform Requirements for

Manuscripts Submitted to Biomedical Journals 

00cientists have an ethical obligation to submit creditable research

Results for publication.  Moreover, as the persons directly

Responsible for their work, scientists should not enter into

Agreements that interfere with their control over the decision to

Publish the papers they write.00/font>

 
 
 

Publication Rights 

Investigator:

          free to publish methods/data/results of study 
 after multi-center publication 
 subject to prior review by sponsor 

Sponsor:

          time-limited right of review (30+ days)

          time-limited right to delay to protect IP

          no right to withhold publication

          no editorial control 
 direct multi-center publication

 
 
 

Intellectual Property Rights 

Sponsor Inventions 
- protected by patent, copyright, trade secret 
- related to Sponsor00 study drug/device/biologic

    - based on Sponsor confidential information 

Institution Inventions 
- protected by patent or copyright 
- invented by Institution employee 
- not directly related to study drug/device/biologic 
 (or new formulation, indication, use) 
- not based on Sponsor confidential information 
- time-limited option to license  
Joint Inventions 
- invented by employees of Institution and Sponsor 
- joint ownership with right to license  
 
 

Indemnification 

Sponsor developed the drug or device Sponsor designed the Protocol / Study Sponsor monitors the Study and data PI/Institution required by Sponsor to follow Protocol and its instructions    

Sponsor should indemnfiy for any injuries

      arising from the study 00.

 
 
 

Indemnification Provision 

Relieves (00old harmless00 Institution (subsidiaries, affiliates, officers, trustees, etc), PI and sub-investigators of any liability (00laims00 resulting from the use or administration of the study drug/device/biologic or arising from a study-required procedure provided:

 
 - protocol and other written instructions of Sponsor are followed;

      - informed consent is obtained from the study patient;

      - all applicable FDA or other gov00 requirements are followed;

      - no negligence or willful misconduct on part of PI or Institution;

      - timely notification of a complaint 

 
 
 

Clinical Research Review Process 

Regulatory compliance 
- IRB reviews & approves ALL clinical protocols 
- Radiation Safety Committee approval for other than standard  clinical use of radiation 
- Health & Environmental Safety (EHS) 
- Biosafety & Biohazards (IBC) Institution 
- SPA reviews and negotiates all CRA/CTAs in accordance with  University policies 
- Clinical Research Office/Dept/PI approves budget 
- Legal has final approval  
 
 

Clinical Research Partnerships 

Rx Sponsors

Regulatory Approval Publications Enhanced Healthcare Sales & Profits  

CROs/SMOs/Monitors

Fee for Service Expand research capability Work satisfaction  

AMCs/Investigators

Fee for Service Expand research capability Academic interest/recognition Publications Training & special services Patient care alternatives  

Patients

Improved care Decreased expenses New therapies Contribute to science  

BENEFITS

 
 
 

Master Clinical Trial Agreements 

GlaxoSmithKline Merck Novartis Wyeth  

Study Specific Document

 
 
 

Investigator Code of Conduct 

Investigators will make sound, ethical decisions as they intereact with patients, Sponsors, regulatory agencies, their staff and Company00 employees Investigators will have a thorough understanding of all applicable laws and regulations, Good Clinical Practices, ICH requirements, IRB Committee reviews and informed consent requirements, and will scrupulously comply with them. Investigators will have a thorough understanding of the scope and purpose of the study, and will only participate in studies within their scope of practice and area of medical expertise. Investigators will protect the safety of each study subject.  
 
 

Code of Conduct (cont00) 

Investigators will respect the rights of the study subjects with regard to their health care decisions, involvement in the study and the privacy of their health care information. Investigators will communicate openly with Company as to the details and progress of the Study. Investigators have a responsibility to understand the impact of financial incentives on their actions and to recognize how financial incentives give rise to conflicts. Investigators will have the appropriate mechanisms in place for proper recordkeeping and accounting throughout the study. Investigators must remain personally accountable for the recommendations they make to patients regarding enrollment in clinical trials and the care the patients receive.  

From Investigator00 Agreement of a Sponsor 

 
 
 

That00 it!

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