ORIENTATION FOR NEW CLINICAL RESEARCH

COORDINATORS

Presented by

NC TraCS InstituteUNC 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) DOCUMENTS

Valorie BuchholzAssociate Director for Clinical Trial Quality AssuranceOffice of Clinical Trials

Mornings in the Regulatory World

What Types of Trials Should Meet GCP Guidelines?

• FDA Regulated Trials

• Federally funded (NIH) TrialsRequirement 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 InvestigatorIDE Trials –Investigator Agreement

Documentation for Investigators and Sub-

Investigators

Curriculum Vitae

• Documents qualifications and eligibility to conduct trial

Licensure

• Documents eligibility to provide medical supervision of subjects

Certifications

• Documents qualifications to perform tasks as delegated

GCP 2.8, 4.1.1, 4.1.5

AND MORE……

APPROVAL DOCUMENTS

• Institutional Review Board

• Regulatory Authorities• Protocol Review

Committee• Institutional Biosafety

Committee• Scientific Review

Committee

AGREEMENTS

• 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……

Lab

Info

Normal Ranges

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

1572 /InvestigatorAgreement

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

Laboratory Accreditations (CLIA/CAP)

UPDATE

GCP 8.2.11-12, 8.3.1, 8.3.6

Update

IRB renewals /

modifications

Regulatory Authorities

Biosafety CommitteeProtocol Review

Committee

CV’s / Licensures / Certifications

for New Investigators

GCP 8.3.2-5

ADD

LOGS

DELEGATION OF

AUTHORITYLOG /

SIGNATURESHEET

SCREENINGLOG

SUBJECTENROLL-

MENTLOG

SUBJECTID CODE

LIST

TRAINING

LOGSProtocol

IBEquipment

CRF Completio

n / Correction

RETAINED

BODYFLUID

/ TISSU

ESAMPLES

GCP 4.1.5, 4.2.4, 8.3.20-22,

INCLUDELetters

Meeting Notes

Telephone Calls

Memos to File

REL

EVA

NT

CO

MM

UN

ICAT

ION

S

GCP 8.3.11

SAFETYSERIOUS ADVERSE

EVENTS• Report to sponsor and IRB

UNANTICIPATED / UNEXPECTED

ADVERSE EVENTS• Report to Sponsor and IRB

SAFETYINFORMATION /

REPORTS• Sponsors Notify Sites

STUDY COMPLETION LogsInvestigational Product AccountabilitySubject Identification Code

Final Close-out monitoring report Includes where site documents will be stored

Termination of study with IRBClinical 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 RequirementsDepends on the Type of Trial

• FDA: 21CFR312.62 (IND) OR 21CFR812.140 (IDE)

• Contracts with Funding Source

• Institutional Policies: http://library.unc.edu/wp-content/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/ucm073122.pdf

FROM CDA TO STUDY CLOSUREPanel Members:

Christine NelsonVal 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/ICF checked for Consistency

eIPF completed in Ramses

Account Number Assigned

Conflict of Interest eForm

completed

Study Information is pushed to EPIC

via CRMS

Billing Calendar

Built in Epic

CTA Executed

CTA Executed

Prepare for/Enroll Subjects

Enrollment Complete

Site Initiation

Visit

Study Closure

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

tired…

Mornings in the Regulatory World

What Types of Trials Should Meet GCP Guidelines?

• FDA Regulated Trials

• Federally funded (NIH) TrialsRequirement 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)

BEFORE STUDY IS INITIATED:

Investigative Site Sponsor/Funding Agency

Documentation for Investigators and Sub-

Investigators

Curriculum Vitae

• Documents qualifications and eligibility to conduct trial

Licensure

• Documents eligibility to provide medical supervision of subjects

Certifications

• Documents qualifications to perform tasks as delegated

GCP 2.8, 4.1.1, 4.1.5

AND MORE……

APPROVAL DOCUMENTS

• Institutional Review Board

• Regulatory Authorities• Protocol Review

Committee• Institutional Biosafety

Committee• Scientific Review

Committee

AGREEMENTS

• 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……

Lab

Info

Normal Ranges

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

Include:

LOGS

DELEGATIONOF

AUTHORITYLOG /

SIGNATURESHEET

SCREENINGLOG

SUBJECTENROLL-

MENTLOG

SUBJECTID CODE

LIST

TRAININGLOGS

ProtocolIB

EquipmentCRF

Completion / Correction

OTHERLOGS

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

1572 /InvestigatorAgreement

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

Laboratory Accreditations (CLIA/CAP)

UPDATE

GCP 8.2.11-12, 8.3.1, 8.3.6

Update

IRB renewals /

modifications

Regulatory Authorities

Biosafety CommitteeProtocol Review

Committee

CV’s / Licensures / Certifications

for New Investigators

GCP 8.3.2-5

INCLUDELetters

Meeting Notes

Telephone Calls

Memos to File

REL

EVA

NT

CO

MM

UN

ICAT

ION

S

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 completeData lock / IRB closureLogsInvestigational Product AccountabilitySubject Identification Code

Final Close-out monitoring report Includes where site documents will be stored

Clinical Study ReportPack up the records Pat yourself on the back

Record Retention RequirementsDepends on the Type of Trial

• FDA: 21CFR312.62 (IND) OR 21CFR812.140 (IDE)

• Contracts with Funding Source

• Institutional Policies: http://library.unc.edu/wp-content/uploads/2016/06/unc_ret_sched.pdf

(see Section 6 – Grants and Research Records)

Pediatric Studies – UNC Healthcare Policy?

GCP 5.5.12

Audits –FDA or Sponsor• Who do you call?

• Hint – its not Ghost Busters!

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

TAKE AWAY POINTS

Organized

Consistent

ENTER NEXT Training

November XX, 2017, 12 noon –1:30pm

Brinkhous-Bullitt Bldg, Room 219