ORIENTATION FOR NEW CLINICAL RESEARCH ... - … · ORIENTATION FOR NEW CLINICAL RESEARCH PERSONNEL WEEK 1 Presented by NC TraCS Institute. UNC Office of Clinical Trials. UNC Network

ORIENTATION FOR NEW CLINICAL RESEARCH PERSONNEL

WEEK 1

Presented by

NC TraCS InstituteUNC Office of Clinical Trials

UNC Network for Research Professionals

Overall Agenda for OrientationWeek 1 –• Introduction to the series, NCRP and educational programs, Running a clinical

trial beginning to endWeek 2 –• UNC Institutional Review Board Processes, Conflict of InterestWeek 3 –• Good Clinical Practice and Study Documentation, Informed Consent Processes,

Research Monitor AccessWeek 4 –• Contracts and Clinical Trial Agreements, Billing Coverage Analysis, Budgeting

and Accounting of Research Funds, Preparing and Executing NIH BudgetsWeek 5 –• Study Startup and Roles of Research Personnel, Recruitment Services and CDW,

UNC Investigational Drug Services, Investigational Device Management PolicyWeek 6 –• Investigator-Initiated Study Processes, ClinicalTrials.gov and ICMJE

requirements, Investigational Drug and Device studies at UNC

Overall Objectives• Discuss options available for training/education of research personnel• Review human subject research protection and the IRB• Define appropriate responsibilities for study team members• Describe steps for successful implementation of a study • Describe appropriate management of study documentation • Define Good Clinical Practices (GCP)• Review the informed consent process, including HIPAA• Discuss compliance, essential documents & UNC drug/device policies• Review basic elements of contract negotiation and grant management• Understand policies on disseminating research via ClinicalTrials.gov• Review process for preparing a billing coverage analysis• Describe steps for managing budgets and accounting of funds• Describe steps for preparing and executing NIH grant budgets• Describe good recruitment practices and support available at UNC• Understand policies and implications of conflict of interest• Describe how to implement a clinical trial from CDA to study closure• Understand when an IND or IDE submission to FDA is required

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These are the objectives for the entire 6 week orientation. By the end of the 6 weeks, you should be familiar with a wide range of policies and requirements and good practice related to clinical research and become familiar with the various campus programs and offices that can help you.

Speaker Office/Department Phone number Email

Catherine Barnes RCMU 919-843-0020 [email protected]

Laura Viera NC TraCS / RCMU 919-843-4604 [email protected]

Mike Matamoros OHRE / IRB 919-966-3113 [email protected]

Erika Hanami NRP 984-974-3669 [email protected]

Valorie Buchholz OCT / QA 919-445-9355 [email protected]

Terry Hartman Radiology 919-966-4997 [email protected]

Christine Nelson OCT 919-843-0832 [email protected]

Dana Gatz OIC - Contracts 919-843-0833 [email protected]

Monica Coudurier OCT / CT.gov 919-843-2333 [email protected]

Andrea Eiring OCT / BCA 919-843-2698 [email protected]

Jill Cunnup Budgeting 919-966-0134 [email protected]

Joy Bryde COI office 919-843-5328 [email protected]

Emily Olsson Recruitment 919-966-6274 [email protected]

Andrew Thorne Investigational Drug 984-9740040 [email protected]

Sandy Barnhart Ophthalmology 919 843-0076 [email protected]

Amanda Wood IND/IDE Support 919-843-9445 [email protected]

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Here is a list of the various speakers and the offices they represent (or area of expertise), and their contact information. We recognize that all of the information we present may be a bit overwhelming to someone new here at UNC as there is so much to take in, so we hope that you will at least take away the knowledge of who to contact should issues or problems arise during your research and you suddenly have questions or need help.

mailto:[email protected]
















Knowing the Resources AvailableTopic Unit/Office Website Telephone

Clinical Research Management System CRMS https://irbis.research.unc.edu/crms/ 919-843-1629

Clinical research support NC TraCS Institute http://tracs.unc.edu/ 919-966-6022

Clinical Research Unit CTRC http://tracs.unc.edu/index.php/services/ctrc 919-843-1070

Clinical Trials, QI Program, CT.gov Office of Clinical Trials http://research.unc.edu/offices/clinical-trials/ 919-843-2698

COI & Research Compliance Research Compliance Program http://research.unc.edu/offices/research-compliance-program/index.htm 919-843-9953

Conflict of Interest Training COI Office https://apps.research.unc.edu/coi-training/ 919-843-9953

Contracting for Clinical Trials, BCA, DUAs Office of Industry Contracting http://research.unc.edu/offices/oic/ (919) 962-3630

Data and Safety Monitoring Boards TraCS DSMB http://tracs.unc.edu/index.php/services/regulatory/data-and-safety-monitoring-board 919-966-6844

Hazardous Material Shipping, Safety Training Environmental Health and Safety http://ehs.unc.edu/workplace-safety/ 919-962-5507

HIPAA Policies, Training HIPAA online Training http://www.med.unc.edu/security/hipaa n/a

Human subjects Office of Human Research Ethics (OHRE) http://research.unc.edu/offices/human-research-ethics/ 919-966-3113

Human subjects, GCP, and RCR training CITI on-line program https://www.citiprogram.org/ n/a

IND/IDE Guidance TraCS IND/IDE Program http://tracs.unc.edu/index.php/services/regulatory/ind-and-ide-application-support 919-843-9445

Investigational Drugs Investigational Drug Service (IDS) http://pharmacy.intranet.unchealthcare.org/services/investdrugs 919-843-9919

Laboratory Assays for research UNC Core Labs http://www.med.unc.edu/corefacilities n/a

Learning Exchange Research Compliance Learning Community http://researchcompliance.web.unc.edu/about-learning-exchange/ n/a

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Hopefully you all picked a copy of this handout??? This is a list of resources that can be very handy. It is up to you to know what you need to know to conduct a quality study and know enough to go find the help when you are not familiar enough with a subject. There are a lot of resources here on campus to help you. We will cover some of these offices in the orientation, but definitely not all of them. So, please keep this list nearby and don’t hesitate to reach out when you have a question or need guidance or look up information on these websites. I’m always available to answer questions or offer guidance. And, research central (second from the top) and the NRP websites are very helpful.

https://irbis.research.unc.edu/crms/

http://tracs.unc.edu/

http://tracs.unc.edu/index.php/services/ctrc

http://research.unc.edu/offices/clinical-trials/

http://research.unc.edu/offices/research-compliance-program/index.htm

https://apps.research.unc.edu/coi-training/

http://research.unc.edu/offices/oic/

http://tracs.unc.edu/index.php/services/regulatory/data-and-safety-monitoring-board

http://ehs.unc.edu/workplace-safety/

http://www.med.unc.edu/security/hipaa

http://research.unc.edu/offices/human-research-ethics/

https://www.citiprogram.org/

http://tracs.unc.edu/index.php/services/regulatory/ind-and-ide-application-support

http://pharmacy.intranet.unchealthcare.org/services/investdrugs

http://www.med.unc.edu/corefacilities

http://researchcompliance.web.unc.edu/about-learning-exchange/

Who should attend Orientation?• Personnel involved in clinical research

• Study coordinator• Social / Clinical research assistant• Research nurse• Research associate• Regulatory personnel• Investigators

• Involved in any type of clinical research• Clinical trials• Investigator initiated research• Federal grants• Social / behavioral research

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I’m curious who we have in the audience? How many of you consider yourselves a study coordinator, …….., investigators? Anyone I missed? And, what kind of research do you all do – clinical trials? Invest. Initiated? Grants? Behavioral? Whether the research you do is a clinical trial, a federal grant or investigator initiated - you should gain something from attending this orientation. The content we will provide will be applicable to most everyone who conducts research in humans. Title of this training is orientation for new staff, but it is also useful for old staff who are in new roles in research or need a refresher.

Training, Training, TrainingWell educated study personnel are key to conducting quality research!

• Knowledge of research best practices, good clinical practices, regulatory requirements

• Keeping abreast of current rules, policies, requirements is key to conducting quality research.

• You need to take responsibility for staying informed and educatedRecommended / Required Trainings https://research.unc.edu/human-research-ethics/getting-started/training/• CITI Training – Log in with your Onyen from the OHRE website.

Determine which group of modules is appropriate for your role. Successful completion of the course will be linked to your PID.

• Epic / BCA training (Research Admin 100) – via Hospital LMS system

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There is a lot to learn about how best to conduct research, what are the best practices, the regulatory requirements that differ depending on the type of research you do, and changes to requirements. Training is key to keeping abreast and so it’s good you are here in this orientation to begin learning how to conduct high quality research. How many of you completed the pre-requisites for this orientation? Hands? If you read the fine print, both the GCP and Ethics courses offered through the CITI program were required training before attending this orientation. We can’t teach everything there is to know about research and these 2 courses provide important background for you. If you haven’t taken them yet, try to do them before next week’s class. And, keep in mind that GCP training is now required if you are working with clinical trials. I’ve also listed the Epic/BCA training that is not provided through this course. It has it’s own separate training.

https://research.unc.edu/human-research-ethics/getting-started/training/

More on CITI TrainingThe Human Subjects Protection modules are grouped by categories of research. You only need to complete one group of modules. If in doubt, ask your IRB.

Group 1: Biomedical Research: Medical, physiological or pharmacological studies that typically involve direct contact with subjects. Includes, but is not limited to, research with drugs, devices or other interventions.Group 2: Social and Behavioral Research: Studies on sociological, psychological, anthropological or educational phenomena that typically involve direct contact with subjects. Does not include drug or device studies.Group 3: Data and Specimens ONLY: No direct contact with human subjects. Research limited to use of records, data (including secondary data sets), or biological samples.

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More on CITI Training• Effective January 1, 2017, CITI Good Clinical Practice (GCP)

training is additionally required of all UNC-CH investigators and research staff who are involved in the design, conduct, or reporting of clinical trials involving human subjects. A refresher course will be required every three years. The GCP training requirement is in addition to the OHRE requirement for Human Research Ethics Training (CITI Human Subjects Research Protection modules).

• If you have further questions regarding the required training, please contact the Office of Clinical Trials at [email protected](mailto:[email protected]) or (919) 843-2698.

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Additional Resources• The Office of Clinical Trials has two new education and

training opportunities available through the CITI Training Program:• “Clinical Research Coordinator (CRC) – Foundations”• “Clinical Research Coordinator (CRC) – Advanced”

https://research.unc.edu/clinical-trials/training/citi/

• Research Compliance Learning Community• http://researchcompliance.web.unc.edu/

• Also, see the University Standard on Research Code of Conduct at https://unc.policystat.com/policy/4488529/latest/

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This is an another resource that can be very helpful to you. The Research Compliance learning Community started up a year ago by Lisa Ross with input from Research Coordinators like you. They have a terrific website with lots of information about conducting research at UNC. You should also take a look at the University’s recently released Code of Conduct. CITI = Collaborative Institutional Training Initiative

https://research.unc.edu/clinical-trials/training/citi/

http://researchcompliance.web.unc.edu/

https://unc.policystat.com/policy/4488529/latest/

STUDY COORDINATOR EDUCATIONTerry Hartman, MPH, MS, CCRCClinical Research Manager, RadiologyChair, Network for Research Professionals

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Clinical Research Coordinator and Chair of NRP (Network for Research Professionals)

Why Coordinator Education?

Responsibility of the investigator to ensure that any individual to whom a task is delegated is qualified by education, training and experience (and state licensure where relevant) to perform the delegated task.

Documentation of training is essential for meeting the guidelines put forth by regulatory agencies for the conduct of Human Subject Research.

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Appropriate delegation is primarily an issue for tasks considered to be clinical or medical in nature, such as evaluating study subjects to assess clinical response to an investigational therapy. The investigator (or in some cases the department, division, center) should maintain a list of appropriately qualified person to whom significant duties have been delegated.

Study Coordinator EducationDocumentation of coordinator education may be part of the investigator/ department/division/center processes. This may include (dependent on type of research being conducted):

• Completion of Human Research Ethics Training• Completion of Good Clinical Practices Training• CV and/or state licensure• Job Skill Training (such as conducting an EKG)• Training plan per your specific job title• Documentation of Training for each protocol

(training logs)• Informed consent training

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The investigator (or department/division/center) should have a list that identifies the training that individuals received that qualifies them to perform the delegated tasks. The amount of require education / training will vary greatly depending on the type of research you conduct. For those of you who conduct social/behavioral research – having a file with CV and documentation of Human Research Ethics Training may be sufficient to meet the guidelines. For those of you who conduct clinical research – much more extensive training/education records are needed to adequately meet the requirements set forth through GCP (Good Clinical Practices).

Example: Training & Education Checklist

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Important to document the training! Proof that staff are qualified and trained for the specific research roles (i.e. Consent Process). This is an example of a training log from the Diabetes Care Center. RN – not generally training in RESEARCH consent by previous work on a hospital floor.

Example Matrix of Training

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Another example that shows who (MD, PA, Nurse) is trained or has qualification to perform the various activities – obviously only certain medically trained individuals can perform a physical exam (need licensure from NC so can’t be a foreign MD who is not licensed here).

Study Coordinator EducationOHRP – Office of Human Research Protection

Responsibilities of UNC• Before any human subjects research can be conducted, the

institution must provide the department or agency a written Assurance that it will comply with the requirements of the Policy

www.hhs.gov/orhp/• The HHS regulations are intended to implement the basic ethical

principals governing the conduct of human subject research

General ResponsibilitiesAll parties involved, institution, investigator, and IRB must actively engage in ensuring human subject protection and this is only achieved through proper training/education of all research professionals

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The Office for Human Research Protections (OHRP) is responsible for the protection of the rights, welfare, and well-being of subjects involved in research conducted or supported by the U.S. Department of Health and Human Services (HHS). OHRP mandates that UNC provide an assurance that it will comply with requirements of OHRP policies – a copy of our federal assurance can be located on the UNC IRB website. The bottom line is proper training in all aspects of the conduct of research is needed to maintain the high standards set forth by the regulatory agencies. The University is currently in process of creating training programs and courses such as this one to help achieve this goal and in addition through the support of the University the Network of Clinical Research Professionals has been formed, whose primary focus is coordinator education.

http://www.hhs.gov/orhp

Mission: To foster a distinguished research community among UNC-Chapel Hill and its affiliates through

education, communication, and collaboration

Vision: To engage and empower individual research personnel at UNC-Chapel Hill and its affiliates,

creating a collaborative and preeminent research community

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A few years ago, Vice Chancellor of Research, Barbara Entwistle, created a Task Force to review the processes for conducting clinical research on campus. The task force met for 6 months and developed a list of recommendations that are currently being implemented. One recommendation was to create the UNC Network of Clinical Research Professionals. The UNC-NRP is a peer group that is open to all research personnel on campus to help increase awareness and communication of best practices through educational seminars, shared resources, mentoring and networking programs. We are excited to have this forum to facilitate campus-wide improvements in the overall management of clinical, social, and translational research.

NRP Educational Programs• Monthly educational seminars• Peer-to-Peer support for new coordinators• Certification study groups - ACRP & SoCRA• Listserv for all individuals involved in human

subjects research (unc.crc listserv)• Informational emails directed specifically to research

professionals• “Did You Know” emails• Educational opportunities• Contact Terry Hartman to join

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Our educational seminars are generally monthly, 1 hr length, and nearly all offer continuing education credits. Peer-to-Peer support available to coordinators new to role or to anyone who just needs a little extra guidance (1:1 mentoring from experienced coordinator). NRP hosts a certification study group to help coordinators prepare for research certification exam through SoCRA or ACRP – starting this summer (last one highly successful – 89% pass rate). We will host the next certification exam here at UNC in the fall. The NCRP is seeking to have all individuals involved with human subject research belong to the unc.crc list serv. Through the listserv a variety of information will be shared that includes a DID YOU KNOW SERIES, updates from the IRB, currently lots of extremely helpful updates on working in Epic, upcoming NCRP educational and social events and information about best practices. The listserv is a vital tool for resource and knowledge sharing among research professionals on campus.

Current Projects• 2019 NRP Professional Development Award• Hands on education seminars• Improving communication with the UNC research

community• Involving UNC research community in workgroups• 2019 Research Expo• Best Practices for Clinical Research Handbook• Climate Survey

NRP is here for you! Please let us know what you need to do your

job better!

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The NRP is a growing organization, which started 4 years – there is still room to grow. We are updating the NRP website to increase its utility for coordinators. We are organizing a communications committee to help effectively disseminate more information to the coordinator community. Valorie Buchholz is working with a few other coordinators to establish a phlebotomy training course for coordinators, which will be a huge step towards making sure coordinators are qualified and trained for tasks they are responsible for. We are also working closely with the Epic research managers to establish some best practices and put in place simpler guidelines for conducting research involving Epic. We will be hosting some roundtable discussions in the near future to allow coordinators to meet with other coordinators and share their personal challenges and best practices. We are forming a subcommittee specifically for coordinators who conduct social or behavioral research to allow us to provide more relevant resources for that group. As I mentioned earlier, we are hosting certification study groups and will be hosting a SoCRA exam in the fall. We have the ongoing monthly educational seminars.

Final Points…• Please make continuing education a priority• Ensure that the training is documented• Saves time from creating unnecessary errors or having to re-do work

• Things change (i.e.: job duties, policies, procedures)• Elevates the quality of your research• Increased knowledge and skills makes you indispensable to your department

• Wisdom is knowledge applied; must apply what we know.

Who to Contact• To join the list serv, contact Terry Hartman at

[email protected]

• To serve as a volunteer, contact the NRP chair

• Information regarding committees and upcoming events can be found on our web site

www.uncnrp.org


FROM CDA TO STUDY CLOSUREPanel Members:

Christine Nelson

Objectives• Identify the steps for successful clinical trial

implementation from study start up through study closure

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Read objective

Where do I start? • Start by answering a few questions:• Is this a clinical trial?• Who is funding the clinical trial?

• Full proposal • Non-industry (federal, non-profit)• Industry

What is a Clinical Trial?

• NIH: Definition of a Clinical Trial. A research study in which one or more human subjects are prospectively assigned to one or more interventions (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral

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Chris

Decision Tool1. Does the study involve human participants?2. Are the participants prospectively assigned to an

intervention?3. Is the study designed to evaluate the effect of an

intervention on participants?4. Is the effect being evaluated a health-related biomedical

or behavioral outcome?

Confidentiality Agreement

INDUSTRY Clinical Trials Process

Create CRMS Record

Submit CDA review request

to OIC via CRMS

Conduct feasibility assessment

Proceed with clinical trial

End here

Submit to IRB via IRBIS

Includes PRC/SRC submissions, BCA/budget completion

Submit Industry sponsored

agreement to the Industry Contracting

team in OSR via CRMS for

negotiation and execution

Create and submit IPF via RAMSeS

CTA Fully Executed

OCT Completes Compliance Checks:• IRB approval• ICF and CTA consistent Subject injury

language • GCP training current• COI training(current), disclosure and review

on those listed on the IRB application• Second COI training (current), disclosure and

review on those listed on the IPF• BCA Complete if applicable• Budget compared to CTA

OCT creates “packet” for OSR

For Industry Sponsored studies

Only

Packet Includes):• IRB approval letter• Fully executed agreement • Copy of IPF• Copy of review request form

from Alice – Industry Contracting Office

• Screen shots of RAMSeS COI• PS Project ID request form

Protocol Received

OCT Completes Compliance

Checks

OSR Creates PS project ID

Subject Injury Language

given to study team by OCT as applicable

Sponsored Projects Specialist reviews the following:• Confirm PI eligibility• Confirm PI certified IPF• debarment status in Visual Compliance

for all those listed on the IRB application

Final packet reviewed by Sponsored project Manager and sent to Data Management for PS project ID

NO

YES

Full Proposal Solicited or Unsolicited

Full Proposal

Create CRMS Record

Submit CDA request to OIC through CRMS,

If applicable

Protocol Received or

finalized if IIT

Feasibility Assessment completed

Decision to proceed

End here

Create and submit IPF for proposal

Submit to IRB

OCT Completes Compliance Checks:• IRB approval• ICF and agreement consistent Subject injury



review on those listed on the IPF• BCA Complete if applicable

OSR Notifies OCT of Clinical

Trial

OCT Completes Compliance Checks

and notifies OSR

PS project ID assigned

Yes No

Includes SRC/PRC submission, BCA and budget development

Sponsored Projects Specialist reviews the following:• Confirm PI eligibility• Confirm PI certified IPF• Budget review • Review of required components

OSR Negotiates award

Fully Executed agreement/budget

Award Set Up• Check

debarment status

• COI

Final Packet review by Sponsored

Project Manager

Sent to data management for PS

project ID

If agreement specifies an end date, the end date must be used in ConnectCarolina, to extend an amendment is

needed to the agreemnt.

Formal proposal required by sponsor

BCA Completed

So it begins… CDA

• Confidentiality Agreement = CDA

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First sponsor contact can come to the PI, Study coordinator or through various avenues. The sponsor will sometimes ask for a brief site information form to be completed, be aware that these can sometimes have CDA attached to them. You may complete the site information form and Confidentiality Agreement or CDA and never hear back from the sponsor or Contract Research Organization since they may not have a fully developed and FDA approved protocol or as in the case of CRO’s not gotten the contract with the sponsor for the trial. We are seeing less and less sponsors manage their own trials

CDA• CDA submitted via CRMS (maybe)• Can be mutual for PI initiated studies • Cannot be signed by PI• Quick turn around• Not every CDA results in receiving a protocol

• Sponsors and CROs track turn around times

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Reminder, Look at the site feasibility/qualification forms carefully, some sponsors CROs are sticking CDA’s into these forms The confidentiality agreement is a contract that can only be negotiated by the Office of Clinical Trials and must be signed by a designee of the university. The PI cannot sign a CDA and have it be valid.

CRMS Record• Start with CRMS

CRMS to Alice for Industry Contracting

Submit CDA

Site Survey

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

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Can be called many different things by different sponsors or CRO’s May just be fishing for potential sites May not even have a final protocol Some come with a protocol synopsis, usually doesn’t have the exact title, a little generic Will ask questions about the PI, whether or not interested, if not why not Patient population Patient recruitment/ retention stats Does the PI have any issues with the study design based on the synopsis PI and site experience Electronic data capture Monitor space/requirements Freezers Lab supplies Centrifuge Ability to perform certain procedures GCP training FDA Form 483 or warning letter IRB, local or central On and on…

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You have fully executed CDA and now the sponsor or CRO will send you the regulatory packet that includes the final protocol, double check to make sure it doesn’t say DRAFT. Look these documents over carefully. Ask if there might be a amendment to the protocol coming out soon The sponsor or CRO may do a site qualification visit You may receive notice of being selected as a site, usually a letter. Some sponsors are now requiring a study start up agreement and wont send the regulatory packet or let you begin working the study until fully executed

Feasibility Assessment • Conduct a preliminary feasibility assessment

• If PI Initiated work with your PI • 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 • Conduct a Billing Coverage Analysis • Budget Requirements

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Once you have your trial in either CRMS or OnCore you can begin conducting a feasibility assessment Start with the draft ICF, then onto the protocol Do you have enough potential subjects to enroll? Is the study schedule practical, reasonable? How long does the study last? Look for non-routine care items OCT has templates and checklists available for conducting a feasibility assessment OCT has some helpful templates Its expensive to take on a study with no enrollment.

Feasibility Assessment

Available on the OCT website: https://research.unc.edu/clinical-trials/forms/

https://research.unc.edu/clinical-trials/forms/

Decision Time

Proceed with clinical trial

End here

NO

YES

Can be done concurrently

CRMS• ALL CLINICAL TRIALS MUST USE 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 Informed Consent Form (ICF)• Draft Clinical Trial Agreement (CTA)• Draft Budget• Investigator brochure (IB)• Pharmacy manual • Lab manual

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Regulatory packet includes the protocol, draft budget, draft clinical trial agreement or CTA and draft or sponsor model informed consent form. If not in the packet you should request the pharmacy manual, lab manual and investigators brochure. Now is the time to get your study in the clinical trial management system or CTMS. Here at UNC we have two CTMS’s; CRMS or the Clinical Research Management System and OnCore used by oncology only.

Budget• Billing Coverage Analysis – required for all clinical trials with using tests and

procedures performed in the healthcare system • 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

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The BCA is very important and helps document our reasoning for charging the procedure/service to Medicare/insurance or to the study. The justifications for items and services designated as routine need to make sense and reference sources. The BCA starts with the study coordinator, then goes to OCT for a QA review, then onto integrated billing for the applicable codes and costs, these include hospital billing and professional billing. The BCA is then routed back to the study coordinator to complete the budget negotiations with the sponsor. Once complete the BCA needs to be routed to the PI for certification or approval. Once the PI certifies it comes back to OCT for a final check to ensure the BCA is consistent with the contract, budget and informed consent. With the budget, be tough, Industry can and will pay. Its important to understand that by not covering the cost of conducting the trial we are supporting the Pharma industry and jeopardizing our non-profit status They want to work with UNC and UNC investigators. Arielle from our office says “UNC is the pretty girl at the dance and everyone wants to dance with us”

Clinical Trials Agreement • Submit draft clinical trial agreement (CTA) to the Office of Industry

Contracting (OIC) via CRMS, direct link to ALICE• Complete review request form (RRF)

• Contract manager assigned• Only the assigned contract manager negotiates terms and conditions

in the CTA• Department is responsible for negotiating the payment terms and

conditions with the study budget• Maintain 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

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Submit your contract or CTA to OCT via Alice. Once you complete the review request form or RRF it is routed to the PI for certification. The PI is required to answer a few simple questions, after that is done we can assign it to a contract manager at OCT. The PI gets many automated emails asking for “certification” they get them from Conflict of Interest, Ramses, OCT and for the BCA. Sometimes you need to remind your PI’s about moving these along. Only OCT can negotiate the contract, DO NOT send any internal communications regarding contract negotiations to sponsors or CRO’s. There needs to be open communications between the contract manager and coordinator

Subject Injury Language in the Informed Consent • As of April 2018 the UNC has approved standard subject

injury language • OIC is required to obtain certain subject injury language in

the CTA with industry sponsors• Language will be different for PI initiated and Federally or

non-profit funded clinical trials • Current OHRE SOP requires an “official” email to be

included in your submission to an external commercial IRB

• Please email [email protected] with the draft ICF with the standard subject injury language

• I will review and send the “official” email


Standard Subject Injury LanguageWhat will happen if you are injured by this research?

All research involves a chance that something bad might happen to you. If you are hurt, become sick, or develop a reaction from something that was done as part of this study, the researcher will help you get medical care, but the University of North Carolina at Chapel Hill has not set aside funds to pay you for any such injuries, illnesses or reactions, or for the related medical care.

The Sponsor of the study, [INSERT SPONSOR NAME], has agreed to pay all reasonable medical expenses for the treatment of reactions, illnesses or injuries related to the use of the study drug/device, defects in the manufacture of the study drug/device, [select either drug or device]or as a direct result of properly performed study tests and/or procedures, except to the extent such expenses are due to the negligence of the study staff or due to your current disease or condition unless it is made worse because you are taking part in this study.

Standard Subject Injury LanguageThe sponsor has no plans to provide additional financial compensation for lost wages or any other loses or expenses. Any costs for medical expenses not paid by the Sponsor will be billed to you or your insurance company. You may be responsible for any co-payments and your insurance may not cover the costs of study related injuries.

By signing this form, you do not give up your right to seek payment or other rights if you are harmed as a result of being in this study.

If you think you have been injured from taking part in this study, call Dr. (PI Name) at (24 hour phone number). He/she will let you know what you should do.

Standard Subject Injury LanguageIf required by Sponsor, ONLY the following Medicare Reporting language is acceptable:To pay these medical expenses, the Sponsor will need to know some information about you like your name, date of birth, and social security number. This is because the Sponsor has to check to see if you have health care insurance through Medicare, and if so, report to Medicare the payment the Sponsor makes toward your medical expenses. We will not collect your social security number for this purpose unless you are injured and a claim is submitted to the Sponsor to pay medical expenses.

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

Presenter

Presentation Notes

You need both IRB approval and a fully executed CTA to start study, when you receive your approved ICF please read it to ensure there are no mistakes or misspellings. Remember if using a central IRB you need approval from the UNC IRB before submitting to the central IRB.

CTA Fully Executed

OCT Completes Compliance Checks:• IRB approval• ICF and CTA consistent Subject injury



review on those listed on the IPF• BCA Complete if applicable• Budget compared to CTA

OCT creates “packet” for OSR

For Industry

OCT Completes Compliance

Checks

Those pesky compliance checks • OCT Completes Compliance Checks:• IRB approval• ICF and CTA consistent Subject injury language • GCP training current• COI training(current), disclosure and review on those listed on

the IRB application• Second COI training (current), disclosure and review on those

listed on the IPF• BCA Complete if applicable• Budget compared to CTA

Presenter

Presentation Notes

Double check the ICF against the CTA to ensure consistency. The IRB and OCT are also checking. Make sure to review the ICF BEFORE consenting your first subject. You don’t want any surprises when you conduct the consent process.

RAMSeS IPF

Presenter

Presentation Notes

An account number cannot be assigned until the BCA is complete and has been through all 7 seven steps, need to complete the eIPF in Ramses

Checklist for Industry Sponsored CTs• Industry Sponsored Clinical Trial• ☐ Create CRMS record.• ☐ Submit CDA to in the Industry Contracting Office through CRMS. (note: CRMS still has the

OCT listed and not the Industry Contracting).• ☐ Industry Office notifies of fully executed CDA.• ☐ Regulatory packet received from sponsor.• ☐ Conduct feasibility assessment.• ☐ Submit CTA to the Industry Contracting Office for negotiation, PI certifies submission• ☐ Create BCA• ☐ Submit to the Scientific Review Committee or Protocol Review committee as applicable.• ☐ Submit to IRB. • ☐ Create IPF.• ☐ PI certifies IPF. • ☐ OSR will confirm PI Eligibility • ☐ Once all compliance checks completed and agreement executed, PS project ID assigned.

Checklist for Non-Industry Sponsored CTs• Non-Industry Sponsored Clinical Trial• ☐ Create CRMS record.• ☐ Submit CDA to in the Industry Contracting Office through CRMS.• ☐ Industry Office notifies of fully executed CDA.• ☐ Conduct feasibility assessment.• ☐ Submit to the Scientific Review Committee or Protocol Review

committee as applicable.• ☐ Submit to IRB. • ☐ Create IPF.• ☐ PI certifies IPF. • ☐ OSR will confirm PI Eligibility and review budget, and notify OCT for

Compliance checks• ☐ Once all compliance checks completed and agreement executed, PS

project ID assigned

Full Proposal Checklist • Solicited or Unsolicited Full Proposals • ☐ Create and submit IPF.• ☐ PI certifies.• ☐ OSR review.• ☐ Create CRMS record.• ☐ Conduct feasibility assessment.• ☐ Submit to the Scientific Review Committee or Protocol Review

committee as applicable.• ☐ Submit to IRB. • ☐ OSR will confirm PI Eligibility and review budget, and notify

OCT for Compliance checks• ☐ Once all compliance checks completed and agreement

executed, PS project ID assigned

What can you do to help? • Work with the study staff to ensure their COI and GCP training are

current. Keep your own spreadsheet • Read the approved ICF and check for errors as soon as its received.• Check it against the subject injury language you were given, if the IRB

made a clerical error, notify ASAP to get it corrected. • Check the approved ICF against the fully executed CTA and budget• If using an external IRB upload load your approval documents to

IRBIS ASAP • Make sure your IPF has been submitted in RAMSeS• Those listed in the IPF will need second COI disclosure • If you have questions call OCT 919-843-2698

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

tired…

Study Start Up

• Site Initiation Visit (SIV) – Sponsor Driven• Study Start Up Meeting• 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

Presenter

Presentation Notes

Schedule the SIV – try to ensure attendance by the entire study team! Take notes about questions asked and answered. Summarize and then send to the individual who conducted the SIV (sponsor/CRO) as a recap and ADD to your regulatory binder. If not an industry sponsored study – go ahead and schedule your own Site Initiation Meeting with team members to review protocol; roles and responsibilities; drug or device accountability; etc. Make sure to document: attendance and agenda. Make sure you have all the supplies needed to conduct the study – those conducting industry sponsored studies are fortunate in that the sponsor typically sends everything needed. However, for other types of studies, you will be the one who determines what is needed (lab supplies, shipping supplies, binders for regulatory documents, etc). Make sure to activate the study in EPIC. Study subjects are added in CRMS/OnCore and then “pushed” over into EPIC. Remember it might take a few minutes for you to see the subject show up in EPIC Especially for interventional trials, scan the consent document into EPIC for your subjects. This will fulfill the Joint Commission (the hospital accrediting agency) requirement regarding clinical trials documentation. Health Information Management also requires that the HIPAA authorization be uploaded into the MR. Make sure your study drug orders are ready to go with IDS – there’s nothing worse than getting ready to obtain study drug and finding out something still needs to be done with your orders and IDS (either within EPIC or paper orders)! Before you enroll your first subject, figure out how you are going to maintain documents associated with your study subjects. Will you use subject binders/file folders? Just make sure that whatever system you use (especially file folders) that you include the subject information (subject number/initials, etc) on EACH page! This is important in case multiple binders or folders are dropped or mixed up. You’ll be able to readily identify which papers go with which subjects!! How are you going to maintain source documents? Will everything be documented in the medical record? Will you create source documents? JUST REMEMBER THAT SOURCE IS THE FIRST PLACE INFORMATION IS WRITTEN DOWN!!! It can be quite helpful to have a study visit checklist – all the procedures and information that is required by the protocol for that particular visit. It’s also a helpful tool in case someone else has to conduct the visit for you. The FDA has “dinged” investigators on missing labs, procedures – FAILURE TO FOLLOW THE PROTOCOL AS WRITTEN.

Study Start Up

Clinical Trial Billing & Research Compliance Conference 59

• Site Initiation Visit• Study protocol - Reporting AEs and

SAEs• Investigational drugs (storage,

dispensing, destruction, accountability) or any procedures necessary for other types of intervention

• Inclusion/Exclusion criteria of protocol- Patient Enrolment (including withdrawal criteria)

• Case record form completion and error correction

• Protocol compliance and deviation issues

• Quality management

• Study Start Up Meeting• All agree on how to

enroll/register • How to designate a research

subject in the EMR• Billing review process• Roles and responsibilities• Include the PI

Sponsor Driven Site Driven

Study Conduct• Enroll your first subject

• Inclusion/exclusion criteria• ICF

• Documentation of the informed consent process

• Maintenance of Essential Documents

Presenter

Presentation Notes

Make sure you document that all inclusion/exclusion criteria is reviewed for each subject. You may have to have written consent from the subject prior to ensuring all eligibility criteria are met. Most often, you have obtained a partial waiver of HIPAA from the IRB to be able to look at subjects and their medical records to determine if there is information in the chart to begin to verify eligibility. After that, you will need to obtain written consent (for the most part) to proceed. You don’t want to enroll anyone for whom later on you realize they didn’t meet eligibility criteria. This is a subject safety issue as well as a data integrity issue and MUST be reported to the IRB and the sponsor of the study – regardless of funding source. It may be considered a UPIRSO and in fact, if a federal funding source, will most likely have to be reported to federal Office of Human Subjects Protection. It’s helpful to have a checklist of the eligibility criteria and check it off, noting where in the source this information can be found and have the PI or a designated Sub-Investigator sign off. Just make sure it’s timely!! Make sure you are using the correct, most recent IRB approved consent document! During some of the reviews our group (CTQA) has conducted, we have found incorrect versions have been used. Again this is reportable to the IRB as New Safety Information (within 7 days of becoming aware). Please make sure you document the process you used during the consenting of your study subject. OCT has a template on our website that can be adapted for you to use. It also has space for the date AND time written consent was obtained to document no study specific procedures were done to the subject prior to written consent. Complete any additional screening required – again documenting where this information can be found. If your study is a randomized study – make sure you are randomizing according to the protocol schema. Many industry studies use what is called an IVRS or IWRS (interactive voice response system – telephone; or interactive web response system – computer) to randomize. If a drug study, Investigational Drug Services will need the information to be able to dispense drug. If a device study – make sure you’ve reviewed the device SOP on the IRB’s website and are using a device accountability template. IDS does not dispense devices.

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

Presenter

Presentation Notes

Again, very helpful to have study visit checklists to ensure all procedures dictated by protocol (including capture of adverse events and conmeds) are done. Case report forms/electronic data capture – it is important to complete your CRF/EDC submissions timely. Timeframe is typically written into the contract – many times 5-7 business days from the time the visit occurred. It’s important for patient safety as the sponsor checks frequently for outliers in the data to determine if there should be notification of safety issues to the sites. AND most of the time your site doesn’t get paid until the data is entered and source verified by the sponsor!!! If there are items in your study that may be billed to subject’s insurance, please PLEASE please make sure to complete your EPIC billing review every few days. You want to make sure those charges are being accurately sent to the study or to the subject’s insurance. It also ties up revenue for the healthcare system and makes folks cranky Ensure you are tracking your investigational product. For the most part, on campus, IDS will provide drug accountability. There are a few instances where IDS is involved on the periphery, and the study team is responsible. HOWEVER, for device trials, the study team must provide accountability. REGARDLESS of drug or device, the PI has the ultimate responsibility and if, during an FDA audit there is a discrepancy in investigational product, the PI is held accountable – not IDS! Make sure you know your protocol requirements (regardless of whether it’s industry sponsored, federally sponsored, or PI initiated). For any drug or device, there are federal requirements for reporting SAE/AE. This reporting information should be included in the protocol. Any study that has investigational product (IND/IDE) MUST have a monitoring plan. Someone must be monitoring the trials – whether it’s someone in your group for PI intitiated trials or an outside monitor for industry sponsored trials, the study has to be monitored. Different from auditing. Monitoring looks at data on an ongoing basis during the duration of the trial. Auditing looks at data for a specific timepoint. Make sure your study does not lapse with IRB approval. I know this sounds sort of like a “duh” item, but it has happened here and if you have subjects on an investigational product, you will need to have IRB approval to continue to treat them during the lapse! Deviations should be reported to the IRB based on their SOPS – basically, if the deviation has subject safety potential (think subject didn’t meet eligibility criteria) then the timing of reporting is different. Look at the IRBs SOPs for information related to reporting.

• Use checklists whenever possible• Be consistent• Ask questions• Use the resources available to you:

• NRP• NC TraCS• Office of Clinical Trials• Office of Human Research Ethics

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NEXT WEEK!Week 1 –• Introduction to the series, NCRP and educational programs, Running a clinical

trial beginning to endWeek 2 –• UNC Institutional Review Board Processes, Conflict of InterestWeek 3 –• Good Clinical Practice and Study Documentation, Informed Consent Processes,

Research Monitor AccessWeek 4 –• Contracts and Clinical Trial Agreements, Billing Coverage Analysis, Budgeting

and Accounting of Research Funds, Preparing and Executing NIH BudgetsWeek 5 –• Study Startup and Roles of Research Personnel, Recruitment Services and CDW,

UNC Investigational Drug Services, Investigational Device Management PolicyWeek 6 –• Investigator-Initiated Study Processes, ClinicalTrials.gov and ICMJE

requirements, Investigational Drug and Device studies at UNC

Week 1 Evaluation Link:https://tinyurl.com/ybjnm9a3

https://tinyurl.com/ybjnm9a3