Office of Regulatory Affairs & Compliance What to Expect During a Compliance Review

Transcription

1 Office of Regulatory Affairs & Compliance What to Expect During a Compliance Review Frank Estala Research Compliance Manager Clara Vorpahl Senior Research Compliance Specialist

2 Office of Regulatory Affairs & Compliance Conducts compliance reviews in medical billing and research Oversees the Compliance Hotline Privacy Officer/HIPAA Report to the President s Office 26

3 An Active Monitoring & Auditing Program is Important For Maintaining participant and staff safety Protecting the Institution and the Researchers Maintaining data quality Protecting funding Measuring compliance with regulatory requirements Educate Process Improvement

4 OCR Documentation Standards Section Document Requirement/Purpose ED-1 Protocol To document investigator and sponsor agreement to the protocol, amendments and CRFs; and, to document revisions of trial-related documents that take effect during trial: Initial version that the site was registered Amendments and Letters of Amendment Subsequent versions Investigator signature page File Location Reference (GCP and Local) 21CFR312/812 ICH Guidance: E6 GCP, Regulatory Sections 1.44, binder 1.45, 4.5, 5.23, 6, 8.2.2, Sponsor Investigator IND/IDE FDA Regulated X X x Non-FDA Regulated Non- Exempt Human Research Exempt Form C or Protocol IRB Exempt Application ED-2 ED-3 Protocol Training (Training Log) Documentation that trial procedures were reviewed with the investigator and investigator s trial staff: Summary of start-up calls Training meetings (Initiation, Implementation, Investigator Meeting, Teleconference, List of Training Attendees) 1. To document the signatures of individuals using initials in place of a full signature to sign CRFs and source documents. 2. To document the signatures and initials of all persons authorized to make entries and/or corrections on CRFs. Include all site staff engaged in research, such as: Clinicians Physicians Delegation Pharmacists Log/ Data personnel Signature Any other individuals authorized to make entries and/or Log (IRB B-2 corrections on CRFs. Form) 3. Key/log must include: Initials Printed Signature Legal Signature, including first and last name Credentials (if appropriate) 4. To document Principal Investigator delegation of studyrelated task to staff. To outline the roles and responsibilities delegated by the PI to each team member. 21CFR312/812 ICH Guidance: E6 GCP, Sections 4.5, Regulatory 5.23, binder AAHRPP Element: III.2.A; I.1.D; UTHSCSA IRB Investigator s Handbook Regulatory binder ICH Guidance: E6 GCP, Section AAHRPP Elements: III.2.A; III.2.B; VHA Policy Memo ; VHA Handbook c; Handbook of Operating Procedures, Section X X x X X X X IRB Form

5 Internal Compliance Reviews ALL active human research studies are subject to reviews 25

6 Why Me? Risk-Based* At the request of the IRB Voluntary Triggered by an event or complaint 28

7 *Risk Variables Risks to the Subject Risks to the Institution The tool is divided into 5 sections Protocol Risks FDA Risks Budget/Billing Risk IRB Risks PI Risks 30

8 Protocol Risks Trial Phase Sponsor Investigator Locally Developed Plan IRB Risk Recruitment Status External Monitoring Radiation Disclosure Outside Covered Entity Sensitive Nature of Study

9 FDA Risk Use of an FDA regulated article Budget Billing Risk Billing Medicare or Private Insurance Funding Subject Payments

10 IRB Risks Vulnerable Populations UPIRSO/AE Reporting Deviations Waivers of Informed Consent Use External IRB External Reporting (OHRP, FDA)

11 PI Risks PI Research Experience at UTHSCSA PI History of Noncompliance PI workload

12 Collaborative Review Process Notification letter to PI with review tool Entrance meeting/survey Site Visit (usually 2 business days) Summarize findings during site visit follow-up Five days to address issues Exit meeting with PI to discuss remaining findings in draft report Final report of ORA&C Observations PI response to findings (sent to IRB) 29

13 Preparation for Site Visit ORA&C Obtain IRB History Review Protocol and Related Docs Select Subject Charts for SV Location Convenient to PI/Staff Work Independently

14 IRB History IRB Approvals Date of Approval Approval Type Initial IRB Submission Conditional Approval 29-Jul-14 FB N/A N/A ICF ICF English Spanish Version Version Summary of Approvals Approvals Approval/Amendments Investigat or Advertise Protocol Brochure Reconsentment Sites Initial IRB submission conditional approval. N/A N/A N/A N/A N/A Initial IRB Submission Dtd Final Approval 15-Aug-14 Exp 15-Aug-14 N/A Initial IRB submission final approval. 4/23/14 Amendment 1 Dtd 9/25/14 1-Oct-14 Exp 1-Oct-14 N/A Amendment 2 Dtd 10/21/14 27-Oct-14 Exp 27-Oct Oct-14 Edition 3.1 Dtd 2/25/14 N/A N/A Study title updated ZS description to "sodium zirconium cyclosilicate" to be consistent with the US adopted name; increase enrollment from 120 to 200 due to a US FDA request for a less sensitive analysis which necessitated a larger sample size to maintain statistical power; modified the dose stopping rule; removed testing for plasma fasting glucose; administrative changes to Amendm correct version and amendment ent 1 Dtd dates. No subjects enrolled to date. 6/27/14 N/A No N/A N/A Reduces i-stat potassium value and provides updates to animal toxicology data; addition of Spanish translated consent form. Amendm ent 2 Dtd 10/16/14 N/A No N/A N/A Amendment 3 Dtd 11/25/14 19-Dec-14 AA N/A 19-Dec-14 Spanish translation. N/A N/A No N/A N/A UTHSCSA, UHS

15 PI/Study Team Preparation Review OCR Study Doc Standards Policy Review ORA&C Tool Review Your Records Workspace Records Readily Available Enrollment Logs Regulatory Binders (edocs or paper) Subject Charts (separate vs together) Occasional Check-in Schedule Pharmacy Visit Promptly Respond to Findings Maintain Communication Consult with Research Departments

16 Notification

17 Entrance Meeting/Survey

18 Entrance Meeting/Survey

19 Entrance Meeting/Survey

20 Site Visit Regulatory Binders Sponsor Protocol Investigator Brochure Form 1572/1571 Financial Disclosures Delegation of Authority Logs Initial Protocol/Amendment Training Special Procedures Training Current CVs & Licenses IRB Training/Scopes of Practice

21 SV Regulatory Binder Cont. All IRB Action Letters Initial/Contingent Approval Amendments Progress Reports Non-compliance UPIRSOs Administrative Actions Stamped Consent Forms Affiliate Approval Letter (UHS, VA)

22 SV Regulatory Binder Cont. Screening/Enrollment Logs Investigational Product Accountability & Temperature Logs Labs/Specimens Shipment Records Sponsor Safety Reports Monitoring Log & Reports Case Report Form Templates SOP/Manual of Operation

23 SV Subject Charts Signed Consent Form/Reconsents Inclusion/Exclusion Checklist Laboratory Results Test Results (ECG) Completed Data Collection Tools Medical Records Progress Notes

24 SV Subject Charts Cont. Concomitant Medication Logs Adverse Event Log Deviation Log Note to File Explaining Discrepancies Documentation of Payment

25 What Happens After SV? Receive with issues Five business days >Five days issues on draft report Coordinate exit meeting Post draft report on meeting invite Discuss issues during exit meeting Receive final signed report via Follow-up with IRB

26 The Final Report PI/Research Coordinator IRB (Dr. Kim Summers) AVPR (Dr. Joseph Schmelz) Affiliate (UHS Research Office, VA R&D, VA Compliance) Department Chair (if warranted) Compliance Committee UT System

27 Research Observations Scope and Number of Observations of Studies Reviewed Degree of Observations Clinical Trial Billing Reviewed Departments Regulatory and Essential Documents Participant Files/ Informed Consents Protocol Procedures Study/Source Documentation -Case Report Forms Pharmacy/ Drug Accountability Study/Safety Monitoring- Reportable Events- UPIRSOs and Adverse Events Other Number of Critical Number of Major Number of Minor Total PI/Dept. Observations Number of Studies Reviewed Percent Exception Rate Requiring Refund/Rebil l 2 Dept A N/A N/A 3 Dept B N/A N/A

28 Data Trends Dept A Reviewed Department Regulatory and Essential Participant Files/ Documents Informed Consents Legal Authoritive Representative was not specified on the Informed Consent Reportable Events- UPIRSOs and Protocol Deviations Study/Source Documentation- Case Report Forms Pharmacy/Drug Accountability Study/Safety Monitoring- Reporting Other Degree of Observation Minor Dept A Required sponsor training was not documented for approved study staff Minor Dept B Adverse Events were not assessed for Clinical Significance by the Principal Investigator Minor Dept B CRF/Study worksheets were not signed by the person obtaining the study information Minor Dept B Inappropriate corrections were made to the CRF/Study worksheets Minor

29 Consequences of Non-compliance

30 Consequences of Non-compliance Safety risk to participants Jeopardize reliability of study data Negative Publicity Fines & penalties Legal fees & settlement costs Loss of public trust in clinical research Suspend research for PI or whole institution 24

31 Focus Areas & Common Findings 31

32 Regulatory Documents Submit progress reports to IRB on time to prevent lapse in approval Check progress report for errors Comply with reporting requirements for protocol deviations/adverse events/upirsos 34

33 Informed Consent Check IRB stamp for most current consent version date Fill in signatures & time (AM/PM) Obtained by a person approved by IRB Evaluate the need for translation Document consent process in a progress note 35

34 Inclusion/Exclusion Criteria Follow your protocol/plan Document eligibility for participation (i.e. use a check list for inclusion/exclusion criteria) 36

35 Protocol Compliance Follow your protocol/plan Visit/Survey Frequency, Study Forms, Scope of Data, Sites/Locations Submit any amendments to the IRB Track/document deviations or missing data 37

36 Documentation Correct data appropriately Sign and date forms Check for transcription errors from source documents to database or case report forms (CRFs) to sponsor Keep electronic files on a secure server and paper documents in a secure location 38

37 Investigational Product Accountability Drug dispensing/accountability log Maintain temperature/storage log Dispense by a person approved by IRB Have documentation of instructions for Investigational Product use (dispensing, returning & disposal)

38 PI Oversight of Study Local policies Conduct the study as approved by sponsor and IRB Ensure staff is qualified and trained Review adverse events and deviations Be ready for monitoring/inspections 40

39 SELF ASSESSMENT Practicing Good Clinical Practice 41

40 Things change. Be inspection ready! Used with permission from Don Mayne. Wretched Mess Research Cartoons(2009)

41 Self Assessment Basic Questions to Ask: 1. Is it research? Do I need IRB approval? 2. What regulations and policies apply? 3. Am I following the IRB approved protocol/study plan? 42

42 Self Assessment Quality means doing it right when no one is looking Henry Ford Request copy of compliance review tool Review the OCR s Documentation Standards Principal Investigators - Check participant charts and consent forms 43

43 Good Clinical Practice Keep enrollment log up to date Maintain regulatory binder/file Document, document, document! Maintain adverse event and protocol deviation tracking logs Promptly report non-compliance and UPIRSOs to the IRB 44

44 Common Findings Failure to follow the protocol Inadequate and inaccurate records Failure to report adverse events Failure to report concomitant therapy Inadequate drug/device accountability Lack of training/qualifications records Informed consent issues IRB problems (approvals) 9

45 Regulations & Policies FDA Regulations (Title 21 Parts 11, 50, 54, 56, 312, 812) The Common Rule (Title 45 Part 46) Good Clinical Practice (GCP) Sponsor Policies (Industry, HHS) IRB / Institutional Policies AAHRPP HIPAA 3

46 Privacy & HIPAA What do you need to know? Kathy James Assistant Compliance Officer Assistant Privacy Officer

47 HIPAA Incidents Notification to the Privacy Office (ORAC) of any incident IRB will request overview of CAPA by the Privacy Office Information Management Services will assist in review of data storage

48 HIPAA Incidents Accessing a patient record without the need to know for your job (FairWarning audit trail) Discussing subject identity in open areas Sensitive study advertisements with contact not a uthscsa domain Sending subject identifying data external in unencrypted

49 HIPAA Incidents Mobile devices being used to store subject data not encrypted All laptops need encryption-no university data on personal laptops Cell phones with university s need to be password protected and registered with IMS (MDM-Mobile Device Management) 44

50 HIPAA Incidents Posting subject/patient information on social media sites, i.e., Twitter, Facebook, SnapChat, Instagram, etc. More of the 18 identifiers posted than you think Lose of confidence with our subjects Reflects badly on the university

51 HIPAA Incidents Storing research data with subject/patient information on clouds, i.e., DropBox. Clouds not approved by IMS are not secure No automatic back-up and data could be lost Data is not easily retrievable if needed (no administrator)

52 Use of Social Security Numbers Handbook of Operating Procedures Section Required Notices for Disclosure Approved Notices for Disclosure

53 Utilize Resources Attend IRB Forums Visit IRB, CTO (New Clinical Trial Office) and OCR websites for updates, forms, and policies: Documentation%20and%20Data%20Mngt %20v2.1%20w%20Matrix.pdf 45

54 Office of Regulatory Affairs & Compliance ORAC Office: (210) Anonymous Compliance Line Gail Madison-Brown, Kathy James, Frank Estala, Clara Vorpahl, 46

55 Used with permission from Don Mayne. Wretched Mess Research Cartoons(2009)