HCCA Region I-Fall Conference
ADVANCED RESEARCH
COMPLIANCE
F. Lisa Murtha, J.D.
Vice President of Audit, Compliance and Privacy Officer
The Children’s Hospital of Philadelphia
murtha@email.chop.edu
(215) 801-7824
Agenda
Important issues in research today
Risk areas in clinical research compliance
Compliance Officer’s role in research
compliance
Questions?
Important Challenges in Research
Today
OHRP staff turnover
Decentralized nature of research
Federal government funding is unstable
Increased focus of regulators
Unstable financial picture for many
providers and research sites
Advances in use of technology
Increased exposure of IRB members
Risk Areas in Clinical Research
Compliance
Human subject protections
Conflicts of interest and financial disclosures
HIPAA/Privacy
Research billing issues
Research vs. innovative care
Monitoring use of research funds (residual
balances, cost sharing, time and effort reporting,
etc.)
Scientific Misconduct
Human Subject Protections
Tuskegee study opened eyes to abuses in
research
This led to the Belmont Report (respect,
beneficence, justice)
Led to increased monitoring
Led to increased regulation
October 1, 2000-Required education in the
protection of human subjects for all investigators
submitting NIH applications for grants or
proposals
Federal Regulations Governing
Operation of IRBs
Common Rule: Policy for the Protection of
Human Subjects
DHHS Regulations (45 CFR Part 46)
FDA Regulations (Title 21, CFR 50 and
Title 21 CFR 56)
Other federal and state regulations
IOM statements and recommendations
FDA Rules
FDA regulates but does not per se,
support or conduct research
FDA regulations address requirements for
informed consent (21 CFR 50)and IRBs
(21 CFR 56)
FDA regulates research on products,
drugs, devices, and food/color additives
FDA rules apply whether research is
funded by the government or not
FDA Sanctions
Withhold approval
Prohibit enrollment of new subjects
Terminate ongoing studies
Disqualify IRB or parent institution
Refer to OHRP or law enforcement
authorities
Office for Human Research
Protections (OHRP)
OHRP oversees compliance of government
sponsored research
OHRP may:
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Restrict or withdraw assurance
Require re-review or suspension of research
Mandate temporary suspensions
Recommend debarment or suspension from
government contracting
– Refer to FDA findings that affect FDA research
Institutional Review Boards
IRB is a medical staff committee with broad
power in oversight of clinical research
IRB determination within an institution is
considered FINAL
IRB must remain independent
IRB membership (# of members, diversity of
group, community representation, lay
perspective, independent perspective, scientific
perspective)
Conflicts of Interest
Objectives of the Financial Disclosure
Rules for Clinical Investigators (21 CFR
54)
– Alert the IND/NDA sponsor to any potentially
problematic financial interest
– Minimize the potential for study bias
– Facilitate collection of accurate data that may
be submitted later
Disclosable Conflicts
Compensation arrangements that could affect
objectivity of investigator
Ownership (including spouse and dependent
children) interest in product under study
Equity interests in public companies that exceed
$50,000
Equity interests in the sponsor that cannot be
calculated
Significant payments by the sponsor to the
investigator or team (Subject of recent OIG
guidance for pharmaceutical manufacturers)
HIPAA Privacy
From April 14, 2003 forward, all research must
be specifically reviewed from the perspective of
the privacy of the research subject by either an
IRB or Privacy Board, per the HIPAA Privacy
Rule
Providers, payors, clearinghouses and business
associates of other covered entities are subject
to HIPAA
Pharmaceutical companies are NOT covered
entities under HIPAA nor are they business
associates of covered entities
HIPAA Research Requirements
Uses or disclosures of “Protected Health
Information” for research require:
– Signed, HIPAA compliance “authorizations” from each
study participant (which can be combined with the
Informed Consent Document)
– IRB or Privacy Board waivers of some or all of the
authorization requirements
– De-identification of patient data via removing all 18
HIPAA identifiers, statistical analysis or opinion, Or
Limited Data Set
HIPAA Authorizations Must
Be written in plain language and signed by each study
participant
Specify the data that will be collected and each use
Specify the persons or types of persons who will have
access to the data
State the right of refusal and revocation and that existing
data may still be used
State that once the data are provided to the sponsor,
HIPAA will no longer protect them
Disclose any payments from the sponsor to the
investigator for use or disclosure of the data
Limited Data Set
Allowed:
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Admission Dates
Discharge Dates
Service Dates
Death Date
Age (in hours, months or
days
– Age (for those over 90)
– Zip Code
– Gender
Not allowed:
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Names
Address
Telephone/fax
Email address
SSN#
Certificate or License #
Vehicle ID and Serial
Number
– URLs and IP addresses
– Full face photos and
comparable images
Waivers
Use or disclosure involves no more than minimal risk to
patient (similar to CR)
Alteration or waiver will not adversely affect privacy
rights and welfare of individuals (similar to CR)
Research could not practicably be done with alteration or
waiver or without access and use of the PHI (similar to
CR)
Privacy risks are reasonable in relation to benefits
Adequate plan to destroy identifiers
Adequate plan to protect identifiers
Adequate written assurances that PHI will not be reused
or disclosed for other purposes
Reviews or PHI Preparatory to
Research
Reviews of PHI preparatory to research do
NOT require authorizations or waivers
Need to consider what happens when
individuals who are NOT in the workforce
perform the preparatory reviews
Data collected before April 14 may be
used and disclosed for research as long
as the CR is followed
Research Billing Issues
Double billing
Residual funding could be viewed as a
kickback
Finders fees or other incentives could
compromise objectivity
Are $ sufficient to do study
Accounts receivable
Segregation of charges
National Coverage Decision
Effective for items or services furnished on
or after 9/19/00
Medicare will cover routine costs of
qualifying clinical trials and reasonable
and necessary items or services used to
diagnose and treat complications arising
from participation in all clinical trials
URL: http://www.cms.gov/quality/8d2.htm
What are Routine Costs?
All items or services otherwise generally available to
Medicare beneficiaries that are provided in either
experimental or the control arms of a clinical trial,
including items and services that are:
– Typically provided absent a clinical trial (medically necessary)
– Required for the provision of an investigational item or service
– Required for the clinically appropriate monitoring of the effects of
the item or service or the prevention of complications
– Items and services that are medically necessary for diagnosis or
treatment of complications arising from the provision of an
investigational item or service
Non-Covered Costs
The investigational item or service itself
Items or services for which there is no Medicare
benefit or category, or which are statutorily
excluded, or that fall under a national
noncoverage policy
Items or services furnished solely to satisfy data
collection and analysis needs not used in direct
clinical management of the patient
Items and services customarily provided by the
research sponsors free of charge
Research vs. Innovative Care
Recent OHRP actions have challenged
articles in research publications
Cleveland Clinic and others have been
challenged
Publications citing results from studies not
going through IRB procedures could be
vulnerable
Monitoring Use of Research Funds
The OIG and the DOJ continue to focus on
cases of misuse of research funds
Northeastern University (2003) case
involving misuse of funds and time and
effort reporting
Areas of focus (time and effort reporting,
cost sharing, cost transfers and residual
balances in clinical trials)
Scientific Misconduct and
Investigator Fraud
Why:
– Increasing number and complexity of NCEs in
development
– Competition for clinical investigators and
study sites
– Gaining access to patients
– Outsourcing of key clinical development
functions
Clinical Investigator Fraud
Falsification of data
Detecting and preventing fraud
Roles of Clinical Monitors, QA, compliance
officers, and others
Validation of research results
Compliance Officer’s Role in
Research Compliance
Ensure that appropriate policies and procedures
exist (updates occur regularly)
Standardize forms, templates, protocols
Improve lines of communication
Train research professionals regularly
Perform ongoing monitoring of research
activities
Appoint a research compliance officer and a
research compliance oversight committee
Research Compliance Monitoring
Assess and prioritize your risks
Use the 80/20 rule for risk assessment
Develop a research work plan
Perform testing of procedures and billing
to ensure ongoing compliance
Interview investigators and members of
research administration on an ongoing
basis
A Model Research Compliance
Work plan for 2003/2004
Human Subject Protections
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Identify a selection of studies to audit 80/20 rule
Review selection of IRB minutes to ensure quorum
Adverse event reporting
Review time spent on each protocol
Review IRB membership
Review completion of documentation of Informed Consents
Perform real time informed consent monitoring ensuring
understanding or risks, etc.
– Validate that annual OHRP required training took place
– Review oversight of vulnerable subjects
Work plan cont.
Conflicts of Interest
– Review a sample of protocol consent forms to
ensure completion and appropriateness
– Review EVERY institutional conflict of interest
form to ensure completion and
appropriateness
– Review outliers with Conflicts Committee and
Legal
– Report on Conflict of Interest Disclosures to
the Board on an annual basis
Work plan cont.
HIPAA/Privacy
– Review minutes of IRB/Privacy Board meetings to
ensure time spent on privacy review
– Review IRB/Privacy Board policies and procedures
for appropriateness
– Review training documentation to ensure that all
required individuals were trained
– Review a sample of Waivers
– Review to ensure accounting of disclosures under a
waiver and other purposes
Work plan cont.
Research Billing Issues
– Rationale for segregation of charges inconsistent/not
documented
– Study subject complaints
– Procedures/systems insufficient to ensure proper
segregation of research vs. non-research costs
– Review sampling of clinical trial budgets to determine
uses of residual balances and review closing of old
accounts, transfers to discretionary accounts without
review, researcher control of residual balances
Work plan cont.
Research vs. Innovative Care
– Perform ongoing review of investigator
publications to ensure IRB process is
maintained and completed
– Review training to ensure proper
understanding of research