Transcript Document

Ethical Considerations Associated
with Investigator Payments & Patient
Recruitment
Ginger Clasby - EVP, Business Development
Promedica International
Costa Mesa, CA
714-799-1617 x 25
[email protected]
Popular Media Headlines
What the Public Hears…
“Drug Trials Hide Conflicts for Doctors” – NY Times, 1999
“Research for Hire: A Doctor’s Drug Studies Turn into Fraud” NY Times, 1999
“Safety Concerns Halt Oklahoma Research” – NY Times, 2000
“Probes Targeted UCI Researcher” – LA Times, 2006
Background – Drug Development Climate
1990’s Forward
• Managed care’s strong emphasis on cost containment
• Increased industry emphasis on new drug development
(to preserve/increase revenues)
• FDA reforms improve product review efficiencies
Background - Drug Development Climate
Industry’s Tactical Changes
Med school research inefficiencies & patient enrollment
timetables at odds with industry drug development
timelines
• Industry develops private practitioner researchers &
provides significant subject enrollment incentives
• Subject recruitment programs become increasingly
sophisticated
Background - Drug Development Climate
Interesting Statistics
• Industry investment in biomedical R&D increased from
32% in 1980 to 62% in 2000*
• Ave. time from IND to product approval dropped from
9.2 yr (1987 -1989) to 7.2 yr (1999-2001)**
• Investigator grants paid by PhRMA member companies
increased from $3.2 billion (1993) to $12.2 billion
(projected 2005)**
• Currently ~ 50,000 clinical trials taking place in US**
Sources: *Business Week, **Thomson CenterWatch
Typical Investigator Compensation Programs
$$$$$$$$!
• Flat fee for each subject enrolled
Covers cost of exams, treatments, staff time, overhead
• Bonuses paid for subjects enrolled within accelerated
timeframe or above target numbers
• Finder’s fees or gifts for eligible subjects
• Medical writing support
Median US Cost/Patient
$$$$$$$$!
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$9,800
$9,000
$8,900
$4,500
$6,900
$6,500
Oncology trials
CNS trials
Anti-infective trials
Hematology trials
Endocrine trials
Gastrointestinal trials
Fast Track Systems: Industry Study Cost Trends, October
2003
And So
In the Rush to Enroll…
• Subject disqualification criteria may be overlooked
• Subjects may not be given full disclosure regarding trial
objectives
• Subjects may not be given full disclosure regarding
associated risks
• Subjects may be rushed to participate (without given
time to think it over)
Investigator Management
FDA’s Toolbox
• Investigator Agreement – Form 1572
• Financial Disclosure by Clinical Investigators
• FDA Bioresearch Monitoring Program – Clinical Sites,
Sponsors, IRBs
• Application of sanctions in association with violative
behaviors
BUT FDA does not have authority to review financial
agreements
Investigator Management
Sponsor’s Toolbox
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Appropriate financial agreements
Formal investigator training programs
Study monitoring activities
Internal auditing program
Investigator termination from study
Investigator Management
Investigator Agreement – FDA Form 1572
• Commits to conduct study in accordance with protocol,
FDA regulations & IRB conditions
• Commits to ensure informed consent requirements are
met for all subjects (including controls)
• Commits to ensure that IRB reviews & approves study
initially & on a continuing basis
Disregard to terms of agreement may be considered a
criminal offense
Investigator Management
FDA Investigator Financial Disclosure
• Applies to FDA-directed marketing applications only
• No financial arrangements where study outcome may
affect investigator compensation
• Investigator has no proprietary interest in tested
product
• Investigator has no significant equity interest in
company
• Investigator has not received significant payments of
other sorts
Investigator Management
FDA Bioresearch Monitoring Program
• Comprehensive program of on-site inspections & data
audits to monitor all aspects of conduct & reporting of
FDA-regulated research
• Inspections typically include clinical investigators,
IRBs, sponsor &/or CRO
Investigator Management
FDA Sanctions
• Exclusion of questionable quality or integrity data
• Restriction of parties corrupting process through
misconduct of malfeasance
• Notification to affected parties to implement corrective
action
Investigator Management
Investigator Training Programs by Sponsor
• Provide detailed training on protocol implementation,
study-related documentation & GCP
• Provide periodic training throughout study based on
protocol or procedural amendments
• Training should be documented
Investigator Management
Study Monitoring Activities by Sponsor
• Perform study initiation visits
• Perform interim study visits at appropriate intervals
• Perform appropriate study data review to ID protocol
deviations, data inconsistencies, unreported safety
events
• Review IRB submissions & responses
Get technical
Fill in the blanks
Don’t be intimidated
Address nonconformities appropriately
Investigator Management
Internal Audits by Sponsor
• Perform interim site audits by trained auditors
uninvolved in study
Be suspicious
Expect fraud
Investigator Management
Investigator Termination by Sponsor
• Terminate shipment of investigational product
• Terminate investigator participation in study
• Report investigator to FDA
The Role of the IRB
• Responsible for subject rights & welfare
May insist on documentation of GCP training
• Reviews/approves study protocol & consent documents
• Reviews/approves most subject recruitment materials
• Reviews periodic study progress reports
• Reviews serious adverse event reports
21 CFR 50.25
Consent Document Must Include
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Study involves “research”; explains research purpose
Known risks/benefits
Alternative treatments or procedures
Extent to which confidentiality will be maintained
Compensation & medical tx available in event of injury
or illness
• Contact(s) to discuss study/subject rights
• Participation is voluntary
21 CFR 50.25
Add’l Consent Document Language
• Tx may involve unforeseeable risks
• Anticipated circumstances when participation may be
terminated w/o regard to consent
• Additional costs to subject for participation
• Consequences associated with withdrawal of consent
• Commitment to provide info on significant new findings
during study that may affect willingness to participate
• Approximate # of subjects involved
Subject Recruitment Programs
WANTED – Study Subjects NOW!
• Study websites
• Call centers
• Professional referrals
• Community outreach
• In-office awareness materials
• Direct to patient media advertising – newspaper, radio,
TV, bulletin boards, posters, flyers, etc.
• Financial compensation
Subject Recruitment Programs
Print Recruitment Advertising Should Include
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Name & address of investigator or research facility
Condition under study or purpose of research
Summary of criteria used to determine study eligibility
Brief list of participation benefits (including cash)
Time or other commitment required of participants
Location of research & who to contact for further
information
Subject Recruitment Programs
Research Subject Payments
• Payment amount & schedule must be approved by IRB
• Payment amount should be reasonable – not coercive
• Payment schedule should accrue - not contingent on
study completion
IRB Review of Subject Recruitment Materials
Prohibited Practices
• Coercive language
– “New treatment”
– “Free medical treatment”
– “Make $100!”
• Stated or implied certainty of favorable outcome
• Claims of safety or effectiveness
• Claims of equivalence/superiority to other products
Integrity In Corporate Practices
What Industry Can Do
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Be thoughtful about patient eligibility criteria
Be realistic with respect to enrollment timetable
Provide appropriate investigator training & oversight
Follow-up promptly & appropriately on complaints