HCCA Region I-Fall ConferenceHCCA Region I-Fall Conference
ADVANCED RESEARCH ADVANCED RESEARCH COMPLIANCECOMPLIANCE
F. Lisa Murtha, J.D.F. Lisa Murtha, J.D.Vice President of Audit, Compliance and Privacy OfficerVice President of Audit, Compliance and Privacy Officer
The Children’s Hospital of PhiladelphiaThe Children’s Hospital of [email protected]
(215) 801-7824(215) 801-7824
AgendaAgenda
Important issues in research todayImportant issues in research today
Risk areas in clinical research complianceRisk areas in clinical research compliance
Compliance Officer’s role in research Compliance Officer’s role in research compliancecompliance
Questions?Questions?
Important Challenges in Research Important Challenges in Research TodayToday
OHRP staff turnoverOHRP staff turnoverDecentralized nature of researchDecentralized nature of researchFederal government funding is unstableFederal government funding is unstableIncreased focus of regulatorsIncreased focus of regulatorsUnstable financial picture for many Unstable financial picture for many providers and research sitesproviders and research sitesAdvances in use of technology Advances in use of technology Increased exposure of IRB membersIncreased exposure of IRB members
Risk Areas in Clinical Research Risk Areas in Clinical Research ComplianceCompliance
Human subject protectionsHuman subject protections
Conflicts of interest and financial disclosuresConflicts of interest and financial disclosures
HIPAA/PrivacyHIPAA/Privacy
Research billing issuesResearch billing issues
Research vs. innovative careResearch vs. innovative care
Monitoring use of research funds (residual Monitoring use of research funds (residual balances, cost sharing, time and effort reporting, balances, cost sharing, time and effort reporting, etc.)etc.)
Scientific MisconductScientific Misconduct
Human Subject ProtectionsHuman Subject Protections
Tuskegee study opened eyes to abuses in Tuskegee study opened eyes to abuses in researchresearchThis led to the Belmont Report (respect, This led to the Belmont Report (respect, beneficence, justice) beneficence, justice) Led to increased monitoringLed to increased monitoringLed to increased regulationLed to increased regulationOctober 1, 2000-Required education in the October 1, 2000-Required education in the protection of human subjects for all investigators protection of human subjects for all investigators submitting NIH applications for grants or submitting NIH applications for grants or proposalsproposals
Federal Regulations Governing Federal Regulations Governing Operation of IRBsOperation of IRBs
Common Rule: Policy for the Protection of Common Rule: Policy for the Protection of Human SubjectsHuman Subjects
DHHS Regulations (45 CFR Part 46)DHHS Regulations (45 CFR Part 46)
FDA Regulations (Title 21, CFR 50 and FDA Regulations (Title 21, CFR 50 and Title 21 CFR 56)Title 21 CFR 56)
Other federal and state regulationsOther federal and state regulations
IOM statements and recommendationsIOM statements and recommendations
FDA RulesFDA Rules
FDA regulates but does not per se, FDA regulates but does not per se, support or conduct researchsupport or conduct researchFDA regulations address requirements for FDA regulations address requirements for informed consent (21 CFR 50)and IRBs informed consent (21 CFR 50)and IRBs (21 CFR 56)(21 CFR 56)FDA regulates research on products, FDA regulates research on products, drugs, devices, and food/color additivesdrugs, devices, and food/color additivesFDA rules apply whether research is FDA rules apply whether research is funded by the government or notfunded by the government or not
FDA SanctionsFDA Sanctions
Withhold approvalWithhold approval
Prohibit enrollment of new subjectsProhibit enrollment of new subjects
Terminate ongoing studiesTerminate ongoing studies
Disqualify IRB or parent institutionDisqualify IRB or parent institution
Refer to OHRP or law enforcement Refer to OHRP or law enforcement authoritiesauthorities
Office for Human Research Office for Human Research Protections (OHRP)Protections (OHRP)
OHRP oversees compliance of government OHRP oversees compliance of government sponsored researchsponsored research
OHRP may:OHRP may:– Restrict or withdraw assuranceRestrict or withdraw assurance– Require re-review or suspension of researchRequire re-review or suspension of research– Mandate temporary suspensionsMandate temporary suspensions– Recommend debarment or suspension from Recommend debarment or suspension from
government contractinggovernment contracting– Refer to FDA findings that affect FDA researchRefer to FDA findings that affect FDA research
Institutional Review BoardsInstitutional Review Boards
IRB is a medical staff committee with broad IRB is a medical staff committee with broad power in oversight of clinical researchpower in oversight of clinical research
IRB determination within an institution is IRB determination within an institution is considered FINALconsidered FINAL
IRB must remain independentIRB must remain independent
IRB membership (# of members, diversity of IRB membership (# of members, diversity of group, community representation, lay group, community representation, lay perspective, independent perspective, scientific perspective, independent perspective, scientific perspective)perspective)
Conflicts of InterestConflicts of Interest
Objectives of the Financial Disclosure Objectives of the Financial Disclosure Rules for Clinical Investigators (21 CFR Rules for Clinical Investigators (21 CFR 54)54)– Alert the IND/NDA sponsor to any potentially Alert the IND/NDA sponsor to any potentially
problematic financial interestproblematic financial interest– Minimize the potential for study biasMinimize the potential for study bias– Facilitate collection of accurate data that may Facilitate collection of accurate data that may
be submitted laterbe submitted later
Disclosable ConflictsDisclosable Conflicts
Compensation arrangements that could affect Compensation arrangements that could affect objectivity of investigatorobjectivity of investigatorOwnership (including spouse and dependent Ownership (including spouse and dependent children) interest in product under studychildren) interest in product under studyEquity interests in public companies that exceed Equity interests in public companies that exceed $50,000$50,000Equity interests in the sponsor that cannot be Equity interests in the sponsor that cannot be calculatedcalculatedSignificant payments by the sponsor to the Significant payments by the sponsor to the investigator or team (Subject of recent OIG investigator or team (Subject of recent OIG guidance for pharmaceutical manufacturers)guidance for pharmaceutical manufacturers)
HIPAA Privacy HIPAA Privacy
From April 14, 2003 forward, all research must From April 14, 2003 forward, all research must be specifically reviewed from the perspective of be specifically reviewed from the perspective of the privacy of the research subject by either an the privacy of the research subject by either an IRB or Privacy Board, per the HIPAA Privacy IRB or Privacy Board, per the HIPAA Privacy RuleRuleProviders, payors, clearinghouses and business Providers, payors, clearinghouses and business associates of other covered entities are subject associates of other covered entities are subject to HIPAAto HIPAAPharmaceutical companies are NOT covered Pharmaceutical companies are NOT covered entities under HIPAA nor are they business entities under HIPAA nor are they business associates of covered entitiesassociates of covered entities
HIPAA Research RequirementsHIPAA Research Requirements
Uses or disclosures of “Protected Health Uses or disclosures of “Protected Health Information” for research require:Information” for research require:– Signed, HIPAA compliance “authorizations” from each Signed, HIPAA compliance “authorizations” from each
study participant (which can be combined with the study participant (which can be combined with the Informed Consent Document)Informed Consent Document)
– IRB or Privacy Board waivers of some or all of the IRB or Privacy Board waivers of some or all of the authorization requirementsauthorization requirements
– De-identification of patient data via removing all 18 De-identification of patient data via removing all 18 HIPAA identifiers, statistical analysis or opinion, Or HIPAA identifiers, statistical analysis or opinion, Or Limited Data SetLimited Data Set
HIPAA Authorizations MustHIPAA Authorizations Must
Be written in plain language and signed by each study Be written in plain language and signed by each study participantparticipantSpecify the data that will be collected and each useSpecify the data that will be collected and each useSpecify the persons or types of persons who will have Specify the persons or types of persons who will have access to the dataaccess to the dataState the right of refusal and revocation and that existing State the right of refusal and revocation and that existing data may still be useddata may still be usedState that once the data are provided to the sponsor, State that once the data are provided to the sponsor, HIPAA will no longer protect themHIPAA will no longer protect themDisclose any payments from the sponsor to the Disclose any payments from the sponsor to the investigator for use or disclosure of the datainvestigator for use or disclosure of the data
Limited Data SetLimited Data Set
Allowed:Allowed:– Admission DatesAdmission Dates– Discharge DatesDischarge Dates– Service DatesService Dates– Death DateDeath Date– Age (in hours, months or Age (in hours, months or
daysdays– Age (for those over 90)Age (for those over 90)– Zip CodeZip Code– GenderGender
Not allowed:Not allowed:– NamesNames– AddressAddress– Telephone/faxTelephone/fax– Email addressEmail address– SSN#SSN#– Certificate or License #Certificate or License #– Vehicle ID and Serial Vehicle ID and Serial
NumberNumber– URLs and IP addressesURLs and IP addresses– Full face photos and Full face photos and
comparable imagescomparable images
WaiversWaivers
Use or disclosure involves no more than minimal risk to Use or disclosure involves no more than minimal risk to patient (similar to CR)patient (similar to CR)Alteration or waiver will not adversely affect privacy Alteration or waiver will not adversely affect privacy rights and welfare of individuals (similar to CR)rights and welfare of individuals (similar to CR)Research could not practicably be done with alteration or Research could not practicably be done with alteration or waiver or without access and use of the PHI (similar to waiver or without access and use of the PHI (similar to CR)CR)Privacy risks are reasonable in relation to benefitsPrivacy risks are reasonable in relation to benefitsAdequate plan to destroy identifiersAdequate plan to destroy identifiersAdequate plan to protect identifiersAdequate plan to protect identifiersAdequate written assurances that PHI will not be reused Adequate written assurances that PHI will not be reused or disclosed for other purposesor disclosed for other purposes
Reviews or PHI Preparatory to Reviews or PHI Preparatory to ResearchResearch
Reviews of PHI preparatory to research do Reviews of PHI preparatory to research do NOT require authorizations or waiversNOT require authorizations or waivers
Need to consider what happens when Need to consider what happens when individuals who are NOT in the workforce individuals who are NOT in the workforce perform the preparatory reviewsperform the preparatory reviews
Data collected before April 14 may be Data collected before April 14 may be used and disclosed for research as long used and disclosed for research as long as the CR is followedas the CR is followed
Research Billing IssuesResearch Billing Issues
Double billingDouble billingResidual funding could be viewed as a Residual funding could be viewed as a kickbackkickbackFinders fees or other incentives could Finders fees or other incentives could compromise objectivitycompromise objectivityAre $ sufficient to do studyAre $ sufficient to do studyAccounts receivableAccounts receivableSegregation of chargesSegregation of charges
National Coverage DecisionNational Coverage Decision
Effective for items or services furnished on Effective for items or services furnished on or after 9/19/00or after 9/19/00
Medicare will cover routine costs of Medicare will cover routine costs of qualifying clinical trials and reasonable qualifying clinical trials and reasonable and necessary items or services used to and necessary items or services used to diagnose and treat complications arising diagnose and treat complications arising from participation in all clinical trialsfrom participation in all clinical trials
URL: http://www.cms.gov/quality/8d2.htmURL: http://www.cms.gov/quality/8d2.htm
What are Routine Costs?What are Routine Costs?
All items or services otherwise generally available to All items or services otherwise generally available to Medicare beneficiaries that are provided in either Medicare beneficiaries that are provided in either experimental or the control arms of a clinical trial, experimental or the control arms of a clinical trial, including items and services that are:including items and services that are:– Typically provided absent a clinical trial (medically necessary)Typically provided absent a clinical trial (medically necessary)– Required for the provision of an investigational item or serviceRequired for the provision of an investigational item or service– Required for the clinically appropriate monitoring of the effects of Required for the clinically appropriate monitoring of the effects of
the item or service or the prevention of complicationsthe item or service or the prevention of complications– Items and services that are medically necessary for diagnosis or Items and services that are medically necessary for diagnosis or
treatment of complications arising from the provision of an treatment of complications arising from the provision of an investigational item or serviceinvestigational item or service
Non-Covered CostsNon-Covered Costs
The investigational item or service itselfThe investigational item or service itselfItems or services for which there is no Medicare Items or services for which there is no Medicare benefit or category, or which are statutorily benefit or category, or which are statutorily excluded, or that fall under a national excluded, or that fall under a national noncoverage policynoncoverage policyItems or services furnished solely to satisfy data Items or services furnished solely to satisfy data collection and analysis needs not used in direct collection and analysis needs not used in direct clinical management of the patientclinical management of the patientItems and services customarily provided by the Items and services customarily provided by the research sponsors free of charge research sponsors free of charge
Research vs. Innovative CareResearch vs. Innovative Care
Recent OHRP actions have challenged Recent OHRP actions have challenged articles in research publications articles in research publications
Cleveland Clinic and others have been Cleveland Clinic and others have been challengedchallenged
Publications citing results from studies not Publications citing results from studies not going through IRB procedures could be going through IRB procedures could be vulnerablevulnerable
Monitoring Use of Research FundsMonitoring Use of Research Funds
The OIG and the DOJ continue to focus on The OIG and the DOJ continue to focus on cases of misuse of research fundscases of misuse of research funds
Northeastern University (2003) case Northeastern University (2003) case involving misuse of funds and time and involving misuse of funds and time and effort reportingeffort reporting
Areas of focus (time and effort reporting, Areas of focus (time and effort reporting, cost sharing, cost transfers and residual cost sharing, cost transfers and residual balances in clinical trials)balances in clinical trials)
Scientific Misconduct and Scientific Misconduct and Investigator FraudInvestigator Fraud
Why:Why:– Increasing number and complexity of NCEs in Increasing number and complexity of NCEs in
developmentdevelopment– Competition for clinical investigators and Competition for clinical investigators and
study sitesstudy sites– Gaining access to patientsGaining access to patients– Outsourcing of key clinical development Outsourcing of key clinical development
functionsfunctions
Clinical Investigator FraudClinical Investigator Fraud
Falsification of dataFalsification of data
Detecting and preventing fraudDetecting and preventing fraud
Roles of Clinical Monitors, QA, compliance Roles of Clinical Monitors, QA, compliance officers, and othersofficers, and others
Validation of research resultsValidation of research results
Compliance Officer’s Role in Compliance Officer’s Role in Research ComplianceResearch Compliance
Ensure that appropriate policies and procedures Ensure that appropriate policies and procedures exist (updates occur regularly)exist (updates occur regularly)
Standardize forms, templates, protocolsStandardize forms, templates, protocols
Improve lines of communicationImprove lines of communication
Train research professionals regularlyTrain research professionals regularly
Perform ongoing monitoring of research Perform ongoing monitoring of research activitiesactivities
Appoint a research compliance officer and a Appoint a research compliance officer and a research compliance oversight committeeresearch compliance oversight committee
Research Compliance MonitoringResearch Compliance Monitoring
Assess and prioritize your risksAssess and prioritize your risks
Use the 80/20 rule for risk assessmentUse the 80/20 rule for risk assessment
Develop a research work planDevelop a research work plan
Perform testing of procedures and billing Perform testing of procedures and billing to ensure ongoing complianceto ensure ongoing compliance
Interview investigators and members of Interview investigators and members of research administration on an ongoing research administration on an ongoing basisbasis
A Model Research Compliance A Model Research Compliance Work plan for 2003/2004Work plan for 2003/2004
Human Subject ProtectionsHuman Subject Protections– Identify a selection of studies to audit 80/20 ruleIdentify a selection of studies to audit 80/20 rule– Review selection of IRB minutes to ensure quorumReview selection of IRB minutes to ensure quorum– Adverse event reportingAdverse event reporting– Review time spent on each protocolReview time spent on each protocol– Review IRB membershipReview IRB membership– Review completion of documentation of Informed ConsentsReview completion of documentation of Informed Consents– Perform real time informed consent monitoring ensuring Perform real time informed consent monitoring ensuring
understanding or risks, etc.understanding or risks, etc.– Validate that annual OHRP required training took placeValidate that annual OHRP required training took place– Review oversight of vulnerable subjectsReview oversight of vulnerable subjects
Work plan cont.Work plan cont.
Conflicts of InterestConflicts of Interest– Review a sample of protocol consent forms to Review a sample of protocol consent forms to
ensure completion and appropriatenessensure completion and appropriateness– Review EVERY institutional conflict of interest Review EVERY institutional conflict of interest
form to ensure completion and form to ensure completion and appropriatenessappropriateness
– Review outliers with Conflicts Committee and Review outliers with Conflicts Committee and LegalLegal
– Report on Conflict of Interest Disclosures to Report on Conflict of Interest Disclosures to the Board on an annual basisthe Board on an annual basis
Work plan cont.Work plan cont.
HIPAA/PrivacyHIPAA/Privacy– Review minutes of IRB/Privacy Board meetings to Review minutes of IRB/Privacy Board meetings to
ensure time spent on privacy reviewensure time spent on privacy review– Review IRB/Privacy Board policies and procedures Review IRB/Privacy Board policies and procedures
for appropriatenessfor appropriateness– Review training documentation to ensure that all Review training documentation to ensure that all
required individuals were trainedrequired individuals were trained– Review a sample of WaiversReview a sample of Waivers– Review to ensure accounting of disclosures under a Review to ensure accounting of disclosures under a
waiver and other purposeswaiver and other purposes
Work plan cont.Work plan cont.
Research Billing IssuesResearch Billing Issues– Rationale for segregation of charges inconsistent/not Rationale for segregation of charges inconsistent/not
documenteddocumented– Study subject complaintsStudy subject complaints– Procedures/systems insufficient to ensure proper Procedures/systems insufficient to ensure proper
segregation of research vs. non-research costssegregation of research vs. non-research costs– Review sampling of clinical trial budgets to determine Review sampling of clinical trial budgets to determine
uses of residual balances and review closing of old uses of residual balances and review closing of old accounts, transfers to discretionary accounts without accounts, transfers to discretionary accounts without review, researcher control of residual balancesreview, researcher control of residual balances
Work plan cont.Work plan cont.
Research vs. Innovative CareResearch vs. Innovative Care– Perform ongoing review of investigator Perform ongoing review of investigator
publications to ensure IRB process is publications to ensure IRB process is maintained and completedmaintained and completed
– Review training to ensure proper Review training to ensure proper understanding of researchunderstanding of research
