Presented by NC TraCS Institute UNC Office of Clinical Trials UNC Network for Research Professionals

ORIENTATION FOR NEW CLINICAL RESEARCH COORDINATORS Presented by NC TraCS Institute UNC Office of Clinical Trials UNC Network for Research Professionals

Overall Agenda for Orientation Module 1: Introduction to Clinical Research, Education, and IRB Module 2: Informed Consent, Documentation and GCP, and Study Start up Module 3: Contracting, ClinicalTrials.gov, and Drug/ Device Policies, Conflict of Interest Policy Module 4: Recruitment, Preparing Industry & NIH Grant Budgets, Accounting, Billing Coverage Analysis Module 5: Essential Documents, From CDA to Study Close Out

ESSENTIAL (REGULATORY) Valorie Buchholz DOCUMENTS Associate Director for Clinical Trial Quality Assurance Office of Clinical Trials

Mornings in the Regulatory World

What Types of Trials Should Meet GCP Guidelines? FDA Regulated Trials Federally funded (NIH) Trials Requirement as of January, 2017 A quality research site complies with the ICH Good Clinical Practice guidelines, the accepted international ethical and scientific quality standards for designing, conducting, recording, and reporting trials involving human participants. American Society of Clinical Oncology Statement on Minimum Standards and Exemplary Attributes of Clinical Trial Sites; R. Zion et al; Journal of Clinical Oncology; April 7, 2008

What are Essential Documents? ICH defines Essential Documents as: the documents which individually and collectively permit the evaluation of the conduct of a trial and the quality of the data produced (ICH GCP E6 (R2) 8.1)

GCP Essential Documents Guidance Categorizes documents into 3 sections Defines whether the sponsor, site or both are responsible for maintenance of the documents Reminder If your investigator holds and IND or IDE, he/she also has sponsor responsibilities

BEFORE STUDY IS INITIATED: Investigative Site Sponsor/Funding Agency

IND trials 1572 Statement of Investigator IDE Trials Investigator Agreement

Documentation for Investigators and Sub- Investigators Curriculum Vitae Licensure Certifications Documents qualifications and eligibility to conduct trial Documents eligibility to provide medical supervision of subjects Documents qualifications to perform tasks as delegated GCP 2.8, 4.1.1, 4.1.5

AND MORE APPROVAL DOCUMENTS AGREEMENTS Institutional Review Board Regulatory Authorities Protocol Review Committee Institutional Biosafety Committee Scientific Review Committee Site and Sponsor Site and CRO Financial Aspects Disclosure Forms (FDA) GCP 3.4, 4.5.1, 8.2.4, 8.2.9

AND MORE Normal Ranges Lab Info CLIA CAP CV of Medical Director GCP 8.2.11

JUST A FEW MORE Investigational Product Shipping and Accountability Records Applicable for both Drugs and Devices Procedures for Decoding Blinded Trials used in case of emergency doesn t break blind for others Study Initiation Report Document questions asked during SIV! GCP 8.2.13, 8.2.14, 8.2.15, 8.2.17, 8.2.20

READY, SET, GO! Documents updated during the study UPDATE Laboratory Accreditations (CLIA/CAP) 1572 /Investigator Agreement Only required by FDA if a new protocol is added to the IND and the Investigator is participating OR a new investigator is added Investigator s Brochures Normal values to lab ranges GCP 8.2.11-12, 8.3.1, 8.3.6

Update IRB renewals / modifications Regulatory Authorities Biosafety Committee Protocol Review Committee CV s / Licensures / Certifications for New Investigators GCP 8.3.2-5

ADD LOGS DELEGATIO N OF AUTHORITY LOG / SIGNATURE SHEET SCREENING LOG SUBJECT ENROLL- MENT LOG SUBJECT ID CODE LIST TRAINI NG LOGS Protocol IB Equipment CRF Completio n / Correction RETAI NED BODY FLUID / TISSU E SAMP LES GCP 4.1.5, 4.2.4, 8.3.20-22,

INCLUDE RELEVANT COMMUNICATIO NS Letters Memos to File Meeting Notes Telephone Calls GCP 8.3.11

SAFETY SERIOUS ADVERSE EVENTS Report to sponsor and IRB UNANTICIPATED / UNEXPECTED ADVERSE EVENTS Report to Sponsor and IRB SAFETY INFORMATION / REPORTS Sponsors Notify Sites

STUDY COMPLETION Logs Investigational Product Accountability Subject Identification Code Final Close-out monitoring report Includes where site documents will be stored Termination of study with IRB Clinical Study Report

Inspections and Essential Documents Sponsors and other regulatory agencies look to these documents as part of their processes to confirm the validity of the conduct of the trial and the data collected

Record Retention Requirements Depends on the Type of Trial FDA: 21CFR312.62 (IND) OR 21CFR812.140 (IDE) Contracts with Funding Source Institutional Policies: http://library.unc.edu/wpcontent/uploads/2016/06/unc_ret_sched.pdf (see Section 6 Grants and Research Records) Pediatric Studies UNC Healthcare Policy? GCP 5.5.12

TAKE AWAY POINTS Organized Consistent

For Additional Information http://www.ich.org/products/guidelines/efficacy/ article/efficacy-guidelines.html http://www.fda.gov/downloads/drugs/ guidancecomplianceregulatoryinformation/guidances/ucm 073122.pdf

FROM CDA TO STUDY CLOSURE Panel Members: Christine Nelson Val Buchholz

Objectives Review the steps for successful clinical trial implementation beginning with first sponsor contact through study closure

So it begins

Site Survey Site information form Site Qualification form Site Feasibility form Sponsors and CROs track turn around times

CDA CDA must be submitted via CRMS Cannot be signed by PI Quick turn around Not every CDA results in receiving a protocol Sponsors and CROs track turn around times

CRMS Protocol final or draft? May just send protocol until you are selected as a site May send someone out to do site qualification visit Draft ICF Draft CTA Draft Budget Investigator brochure Pharmacy manual Lab manual

Feasibility Conduct a preliminary feasibility assessment Read the draft ICF Read the protocol Potential enrollment Study schedule (practical, reasonable) Study duration Non-routine care items Imaging Pharmacy Lab/specimens Resources (study coordinator, data manager, 24/7) Adequate staffing Training requirements Special vendor requirements

Budget Billing Coverage Analysis Spreadsheet from CRMS Deemed and Qualified Epic Billing calendar Funding source (federal or industry) Consistent approach Ensure start up fees are sufficient and invoiced Standardized fees Screen fails Monitoring visits Monthly invoicing IDS CTRC

CTA Submit CTA to OIC via CRMS, direct link to ALICE Complete review request form (RRF) Contract manager assigned Only the assigned contract manager negotiates the CTA Open communication with your contract manager The CTA can be negotiated while you negotiate your budget Once budget has been finalized with sponsor we can execute the CTA

IRB Submit when you are sure the PI wants to participate UNC local IRB or Central IRB ICF and contract must be consistent in respect to subject injury, stipends and what has been promised for free to the subjects

CTA and IRB IRB Approval ICF and CTA must be consistent OCT will check but you should also check If inconsistent the ICF will need to be revised

Ramses eipf Internal budget Need an account Set up after all compliance checks are completed by OCT Sent to OSR for final PS project ID assignment COI Individual Institutional

CTA Executed Study Information is pushed to EPIC via CRMS Account Number Assigned Conflict of Interest eform completed eipf completed in Ramses CTA Executed CTA/ICF checked for Consistency Site Initiation Visit Billing Calendar Built in Epic Prepare for/enroll Subjects Enrollment Complete Study Closure

Study Start Up When can I enroll! Its been months and I am already tired

Mornings in the Regulatory World

What are Essential Documents? ICH defines Essential Documents as: The documents which individually and collectively permit the evaluation of the conduct of a trial and the quality of the data produced (ICH GCP E6 (R2) 8.1)

BEFORE STUDY IS INITIATED: Investigative Site Sponsor/Funding Agency

AND MORE APPROVAL DOCUMENTS AGREEMENTS Institutional Review Board Regulatory Authorities Protocol Review Committee Institutional Biosafety Committee Scientific Review Committee Site and Sponsor/Funding Agency Site and CRO Financial Aspects Disclosure Forms (FDA) GCP 3.4, 4.5.1, 8.2.4, 8.2.9

AND MORE Normal Ranges Lab Info CLIA CAP CV of Medical Director GCP 8.2.11

Include: LOGS DELEGATION OF AUTHORITY LOG / SIGNATURE SHEET SCREENING LOG SUBJECT ENROLL- MENT LOG SUBJECT ID CODE LIST TRAINING LOGS Protocol IB Equipment CRF Completion / Correction OTHER LOGS GCP 4.1.5, 4.2.4, 8.3.20-22,

Study Start Up SIV Site Initiation Visit Study supplies CRMS Clinical Research Management System (OnCore for Oncology studies) Epic IDS Investigational Drug Services at UNC Healthcare Subject binders Source documents Study visit checklist

Study Conduct Enroll your first subject Inclusion/exclusion criteria ICF Documentation of the informed consent process Maintenance of Essential Documents

Documents updated during the study UPDATE Laboratory Accreditations (CLIA/CAP) 1572 /Investigator Agreement Only required by FDA if a new protocol is added to the IND and the Investigator is participating OR a new investigator is added Investigator s Brochures Normal values to lab ranges GCP 8.2.11-12, 8.3.1, 8.3.6

Update IRB renewals / modifications Regulatory Authorities Biosafety Committee Protocol Review Committee CV s / Licensures / Certifications for New Investigators GCP 8.3.2-5

INCLUDE RELEVANT COMMUNICATIO NS Letters Memos to File Meeting Notes Telephone Calls GCP 8.3.11

Ongoing conduct of study Study visit checklists Case report forms Epic Billing review Investigational product accountability SAE/AE reporting Monitor Access Annual IRB renewal Amendments Modifications Deviations

STUDY COMPLETION / CLOSE OUT All study subjects complete Data lock / IRB closure Logs Investigational Product Accountability Subject Identification Code Final Close-out monitoring report Includes where site documents will be stored Clinical Study Report Pack up the records Pat yourself on the back

Audits FDA or Sponsor Who do you call? Hint its not Ghost Busters!

TAKE AWAY POINTS Organized Consistent

ENTER NEXT Training November XX, 2017, 12 noon 1:30pm Brinkhous-Bullitt Bldg, Room 219