Is the Company Health Career Agents a Fraud by wvg13389

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									Fraud & Misconduct
at Investigator Sites

 Paul Below
 Clinical Research Consultant
 P. Below Consulting, Inc.

 Chicagoland Chapter ACRP Clinical
 Research Conference & Career Fair
 Schaumburg, IL
 November 10, 2006
Disclosure & Disclaimer
    I have a consulting relationship with the
     following companies:
           MGI Pharma (project management)
           Medical Research Management (training)

    The views expressed here are my own and not
     necessarily those of the clients listed above or
     of the Minnesota Chapter ACRP. I am solely
     responsible for the content of this presentation.
Presentation Topics
    Definition of fraud
    Prevalence
    Famous cases
    Consequences
    Reasons why fraud occurs
    Warning signs/identifiers
    Detection strategies
    Fraud prevention
FDA Definition of Fraud
    Falsification of data in proposing, designing,
     performing, recording, supervising or reviewing
     research, or in reporting research results
    Falsification includes both acts of omission
     (consciously not revealing all data) and
     commission (consciously altering or fabricating
Fraud Definition (cont.)
    Fraud does not include honest error or honest
     differences in opinion
    Deliberate or repeated noncompliance with the
     protocol and GCP can be considered fraud, but
     is considered secondary to falsification of data
Who Commits Fraud?
    Investigators
    Study coordinators
    Data management personnel
    Lab personnel
    IRB staff
    CRAs and sponsor personnel
    FDA
Who Gets Blamed?
             4% 4%
       9%              39%
                                   Study Coordinator
  9%                               Hospital
                                   Office Staff
   9%                              Sub-investigator


                        Source: FDA Presentation, DIA 2000
Prevalence of Fraud
    Difficult to determine but still considered rare
    Reported to significantly impact 1-5% of
     pharmaceutical clinical trials – F. Wells, Reuters
     Health, January 2002
    Only ~3% of FDA inspections uncover serious
     GCP violations resulting in Warning Letters
Prevalence of Fraud (cont.)
    Survey of over 3000 NIH-funded scientists
     published in Nature (June 9, 2005) – “One in
     Three Scientists Confesses to Having Sinned”
    1.5% acknowledged falsification or plagiarism
    15.5% admitted changing design or results in
     response to pressure from a funding source
    12.5% admitted to looking other way when
     colleagues used flawed data
Famous Cases - Investigators
    Robert Fiddes, MD
     Private practice, Whittier, CA – 1997
    Richard Borison, MD and Bruce Diamond, PhD
     Medical College of Georgia – 1998
    Michael McGee, MD
     University of Oklahoma, Tulsa – 2000
    Maria Kirkman (aka Ann Campbell), MD
     Private practice, Alabama – 2003
Robert Fiddes, MD – “Of Mice and Men”, 60 Minutes, April 1, 2001
Case Study - Dr. Fiddes
    Dr. Fiddes was president of a clinical research
     company in Whittier, CA
    Conducted over 200 studies beginning in the
     early 1990’s
    Engaged in extensive fabrication and
     falsification of data
Dr. Fiddes (cont.)
    Removed exclusionary data from medical
     history in patient charts
    Made up fictitious study subjects
    Fabricated lab results by substituting clinical
     specimens and manipulating lab
Dr. Fiddes (cont.)
    Feb. 1997 – Staffers blows the whistle and FDA
     special agents storm the site
    Aug. 1997 – plead guilty to felony charge of
     conspiracy to make false statements to the FDA
    Sept. 1998 – sentenced to 15 months in federal
     prison and ordered to pay $800,000 in
Dr. Fiddes (cont.)
    June 1999 – disqualified as a clinical
     investigator by FDA
    Mar. 2000 – medical license revoked
    Nov. 2002 – debarred by FDA along with three
     study coordinators
Dr. Fiddes and staff on the FDA Debarment List
 Federal Register Notice for
Study Coordinator Debarment
Richard Borison, MD – “Drug Money,” 48 hours, July 31, 2000
Richard Borison, MD – “Drug Money,” 48 hours, July 31, 2000
Bruce Diamond, PhD – “Drug Money,” 48 hours, July 31, 2000
Bruce Diamond, PhD – “The Lessons of Greed,” PharmaVOICE, July 2004
Famous Cases - Coordinators
    Anne Butkovitz
     Pediatric private practice, Newton, MA – 2005
    Paul Kornak
     Stratton VA Medical Center, Albany – 2005
Paul Kornak – “Abuses Endangered Veterans in Cancer Drug Experiments,”
New York Times, February 6, 2005
Consequences of Fraud
    Sponsor – data validity compromised,
     submission jeopardized, additional costs
    Investigator – fines, legal expenses,
     disqualification/debarment, license revocation,
     incarceration, ruined career
    Institution – lawsuits
    Subject – safety at risk, loss of trust in clinical
     trial process
Consequences (cont.)
    Fraudulent investigators are often used by
     multiple sponsors on multiple trials
    A small number of investigators can have a
     broad impact on many NDA submissions
    One fraudulent investigator, Dr. Fiddes, was
     involved in 91 submissions with 47 different
Why Does Fraud Occur?
    Lack of resources (staff, time, subjects)
    Lack of GCP training
    Lack of regulatory oversight
    Laziness
    Loss of interest
    Pressure to perform or to publish
    Money, greed
General Warning Signs
    High staff turnover
    Staff are disgruntled, fearful, anxious,
     depressed, defensive
    High pressure work environment
    Obsession with study payments
    Absent investigators
    Lack of GCP training
    Unusually fast recruitment
Data Identifiers of Fraud
    Implausible trends/patterns:
           100% drug compliance
           Identical lab/ECG results
           No SAEs reported
           Subjects adhering perfectly to a visit
           Perfect efficacy responses for all
Layout the primary efficacy data for all subjects
          at a site to look for trends
Data Identifiers (cont.)
    Site data not consistent with other centers
     (statistical outlier)
    Source records lack an audit trail - no
     signatures and dates of persons completing
    All source records & CRFs completed with the
     same pen
    Perfect diary cards, immaculate CRFs
Source: British Medical Journal; 324, 1193-1194, 2002
Data Identifiers (cont.)
    Subject handwriting and signatures are
     inconsistent across documents (consents,
    Questionable subject visit dates (Sundays,
     holidays, staff vacations)
    Impossible events (eg, subject randomized
     before investigational product even available at
     the site)
Data Identifiers (cont.)
    Subject visits cannot be verified in the medical
     chart or appointment schedule
    Data contains “digit preference” – some digits
     used more frequently than others (0, 5, and
     even digits)
    “Halo” around the date or test value indicating
     the original was obliterated with correction fluid
Detection Strategies
    Expect fraud – start from the assumption that
     records are bogus and work backwards
    Question missing, altered, and/or inconsistent
     data – offer to retrieve records yourself, keep
     pulling on loose ends and see what unravels
    Don’t be intimidated – challenge to explain
     suspicious data
Detection Strategies (cont.)
    Be suspicious of blame shifting –remind the
     investigator that he/she is responsible for study
    Cultivate whistleblowers – pay attention to staff
     complaints, listen to grievances, establish
     rapport, and be approachable
    Many fraud cases uncovered by whistleblowers
    Ethical commitment to report fraud (ACRP):
           Members shall not participate in, condone or be associated
            with dishonesty, fraud or misrepresentation and be
            prepared to draw attention to, or challenge, practices of
            others that are detrimental to GCP or in the breach of
            relevant legal or ethical standards.

    Many institutions have an Office of Compliance
     with reporting hotlines
    US government encourages whistleblowers
     through False Claims Act awards
False Claims Act
    Unlawful to submit a false or fraudulent claim
     for payment to the United States government
    Private citizens who know of people or
     companies defrauding the government may sue
     on the government's behalf (qui tam relator)
    Plaintiff shares in the proceeds of the suit
     (15-30% of amount recovered by government)
    Contains protections for whistleblowers who are
     harassed, threatened, discharged or otherwise
     discriminated against in their employment
Recent False Claims
 Act settlement with
   the Mayo Clinic
  (Rochester, MN)
Other Recent FCA Settlements
    Cornell University
     $4.4 Million (June 2005)
    University of Alabama at Birmingham
     $3.4 Million (April 2005)
    John Hopkins University
     $2.6 Million (June 2004)
    Northwestern University
     $5.5 Million (February 2003)
Cherlynn Mathias - University of Oklahoma
      Melanoma Trial Whistle Blower
Complaints to FDA
    Reporting is encouraged
    All complaints assumed to be credible
    Prioritized evaluation according to subject
     safety concerns
    25% of complaints are evaluated by an
     on-site inspection (audit)
Complaints Categories


20%                                                 19%



      Protocol Violations   Falsification of   Informed Consent Poor AE Reporting    Poor Drug
                                 Data            Noncompliance                      Accountability

                                                                    Source: FDA, CenterWatch
Whistleblower Required Reading
    “How to Blow the Whistle and Still Have a
     Career Afterwards”
     C.K. Gunsalus
     Science and Engineering Ethics; 4, 51-64, 1998
Fraud Prevention
    During pre-study evaluation, sponsors should
     carefully scrutinize sites for interest in the
     study, stability of the staff, investigator/staff
     interactions, workload, and level of training
    Everyone involved in the clinical trial process
     should complete regular GCP training
    CRAs should be expert on the protocol
     particularly with parameters that determine
     eligibility (inclusion/exclusion criteria) and
     primary efficacy endpoints
Fraud Prevention (cont.)
    Sponsors should emphasize their policy on
     fraud at the initiation visit
    Institutions should set-up systems to
     encourage fraud reporting and protect
This presentation and related references
are posted on my corporate website at:
    Kerrin Young, Study Manager, Takeda, &
     Jeri Weigand, Quality Assurance Auditor, 3M
     Pharmaceuticals, for their collaboration in the
     development of this presentation
    Sini Koshy-Hunt, Chicagoland Chapter ACRP
     for the invitation to present
Contact Information
    Office:   (952) 882-4083
    E-mail:

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