PREP Workshop #31: Preparing for Certification As A Clinical Research Coordinator

Presented by:

Natasha Phrsai BS, CCRC Ruby Garzon RN, MSN, CCRN, CCRC Grace Chan RN, BSN, CCRN, CCRC

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CME Disclosure Statement • The Northwell Health adheres to the ACCME’s new Standards for Commercial Support. Any individuals in a position to control the content of a CME activity, including faculty, planners, and managers, are required to disclose all financial relationships with commercial interests. All identified potential conflicts of interest are thoroughly vetted by the Northwell Health for fair balance and scientific objectivity and to ensure appropriateness of patient care recommendations. • Course Director and Course Planner, Kevin Tracey, MD and Tina Chuck, MPH have nothing to disclose. • Natasha Phrsai, Ruby Garzon, and Grace Chan have nothing to disclose.

Objective: Review requirements and possible preparation options for becoming certified as a clinical research coordinator

Topics: ACRP requirements for taking the certification exams

Review the Alliance Coordinator Award Program

Discuss preparation tools, courses and options

Test current knowledge – study review questions

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• Ethical Principles / Informed Consent / Safety: 20% - 25%

• Institutional Review Board / Institutional Ethics Committee (IRB/IEC) Roles and Responsibilities: 7% - 11%

• Clinical Trial Protocol and Protocol Amendments: 4% - 8%

• Investigator Roles and Responsibilities: 28% - 32%

• Sponsor Roles and Responsibilities: 31% - 35%

See Exam Outline

•FDA regulations. You will not be tested on FDA guidance. However, some of the guidance documents published by the FDA may be helpful in explaining concepts.

General knowledge of: • Laboratory terminology, tests, and

procedures • Basic math, including adding, subtracting,

multiplying, dividing, and calculating percentages

Proficiency in the areas of: • Investigational Product Management • Protocol • Safety • Trial Management • Trial Oversight See Detailed Content Outline (DCO) • ICH GCP Guidelines E6, E2A, E8, E9 • Declaration of Helsinki

http://www.socra.org/certification/ccrp-certification-exam/exam-outline http://www.acrpnet.org/PDF/CRC_Handbook.pdf

What is covered in the exam(s)?

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Regulations and Guidance Documents

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Nuremberg Code

Declaration of Helsinki

Belmont Report

•Department of Health and Human Services, Title 45 Public Welfare, Code of Federal Regulations , Part 46 Protection of Human Subjects

DHHS 45 CFR Part 46

Subpart A = Common Rule *

•Protection of Human Subjects (ICF) FDA 21 CFR

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• Institutional Review Boards (IRB) 56 *

•Electronic Records, Electronic Signatures (EMR) 11

•Financial Disclosure by Clinical Investigators (COI) 54

• Investigational New Drug Application (IND) 312

• Investigational Device Exemptions (IDE) 812

•Good Clinical Practice (GCP) ICH GCP Guidelines

E6 •Clinical Safety Data Management: Definitions and Standards for

Expedited Reporting E2A

•General Considerations for Clinical Trials E8

•Statistical Principles for Clinical Trials E9

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Review of ACRP’s Exam •CRC Certified: “CCRC” •Fall 2016 Exam dates: September 8 – October 1, 2016 Applications Open: May 2, 2016 Applications Due: August 15, 2016 Fees: $450 for ACRP members and nonmembers by July 1 2016- EARLY BIRDS

$525 for nonmembers June 16 through August 15 2016

•Spring 2017 Exam dates: February 23 – March 20, 2017 Applications Open: October 17, 2016 Applications Due: February 1, 2017 Fees: $450 for ACRP members and nonmembers by December 1, 2016- EARLY BIRD

$525 for nonmembers December 2, 2016 through February 1, 2017

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http://www.acrpnet.org/PDF/CRC_Handbook.pdf

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Duration: 3 hrs •125 multiple choice questions •Practice based exam with hypothetical scenarios, no trick questions •Approximately 74% of candidates are successful on their first exam attempt. •Scaled score of 600 (800 max.) required to pass indicates that, while a different number of correct answers may be required from one administration to the next, the passing point for all examinations represents the same level of knowledge. Period of Certification: 2 years

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ACRP’s Eligibility Requirements

One of the following: Option 1: RN, Associates, or Bachelor’s or higher, 3000 hrs, documentation of performed essential duties (CV and Job Description) Option 2: Other such as LPN, LVN, Med. Assistant, Lab Technician OR HS diploma, 4500 hrs, documentation of performed essential duties (CV and Job Description)

http://www.acrpnet.org/PDF/CRC_Handbook.pdf

Alliance Coordinator Award Program

Send it to the CTO; SRay@northwell.edu

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Preparation Tools 1. ACRP Certification Exam Preparation Package

(http://www.acrpnet.org/prepareforyourexam) • Exam Practice Exercise • ACRP's new Certification Exam Preparation eLearning Course • Exam Prep Packages

2. RAN Institute Flash Cards: http://www.raninstitute.com/flashcards.php

3. www.mobilizepress.com - 1-2 hour reviews on other ICH documents. Tip: You can purchase these and have unlimited access to use to prepare for the exams.

4. www.raninstitute.com ICH Guidelines: www.ich.org (Go to Work Products/ICH Guidelines/Efficacy Guidelines)

5. Declaration of Helsinki: www.wma.net/en/20activities/10ethics/10helsinki/index.html

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Pharmaschool (free): http://www.pharmaschool.co/resources.asp. Under the general resources there is a “jargonbuster” with key definitions “GCP and Clinical Research Tests” there are various multiple choice quizzes Registered Users can go to “My GCP Zone” to score your quizzes and tell you how you compare to the average user.

*The website is based out of the UK there are some specific questions regarding EU regulations, but overall was found to be extremely helpful.

Preparation Tools

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Preparation Tools/Ideas

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STEP 1: Assess your own professional experience STEP 2: Start early and plan ahead. STEP 3: Schedule your study time. The key is not to memorize what you read, but to understand concepts behind ICH/GCP and best practices in each knowledge category area to supplement your experience in answering questions on the exam. STEP 4: Assemble your study notes in a binder. STEP 5: Choose the methods that are right for YOUR study plan. Choose a mentor or colleague who has more experience in the areas in which you are less familiar and ask him/her to review concepts with you. STEP 6: Stick to your study group’s plan. STEP 7: Don’t panic! Follow the excellent pre-exam advice that the Academy provides, and come to the exam well-rested and prepared.

http://www.acrpnet.org/PDF/CRC_Handbook.pdf

Preparation Ideas

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Exam Preparation – CTO Study Groups?

•Additional prep sessions using RAN Institute Flash Cards •Contact Susan Ray for CTO study groups

•Electronic GCP •Hard-copy box of flash cards

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Test Current Knowledge 16

FAMILY FEUD AT NORTHWELL HEALTH

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Question # 1

A clinical trial is being conducted for hormone replacement. The trial includes a diary. Which of the following would be considered an objective parameter? A. Mood swings

B. Breast tenderness C. Severity of hot flashes D. Episodes of vaginal bleeding

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Answer #1

D. Episodes of vaginal bleeding

An objective symptom can be measured or observed and is not dependent on, or influenced by, the subjects feelings or opinions.

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Question #2 During the monitoring visit, a CRA discusses the following queries with the CRC: Dates of the subject visits recorded as month/day/year instead of day/month/year Subjects’ identification numbers are missing lead-in zeros Weights are recorded as pounds instead of kilograms Discrepancies in the two subjects’ visit dates between source data and CRF entries Which of the following actions should the CRC take? A. Direct the subinvestigator to correct the CRFS B. Correct errors on the CRFs as discovered C. Resolve discrepancies with the PI D. Send the updated CRFs to data management

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Answer #2

B. Correct errors on the CRFs as discovered

Consider the following rationale for each option: A-WRONG transcription errors can be corrected by CRC; B-CORRECT-transcription errors can be corrected by CRC; C-WRONG-

transcription errors can be corrected by CRC; D-WRONG- it is already identified that corrections are needed. It would not

be correct to send unedited CRFs to data management.

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Question #3

A subject is issued 120 tablets and is instructed to take 2 tablets 4 times a day. He returns 88 tablets on the morning of day 9 fasting for laboratory tests. What percent compliant is he? A. 50% B. 64% C. 78% D. 100%

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Answer #3

A. 50% Math Calculation: 120= #dispensed,

120-88 (#returned)= 32 (number actually taken), 8 days x 8 tablets per day= 64 (# that should have been taken)

32(#taken)/64 (#should have taken) = 0.5 or 50%

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Question#4 A subject is participating in a clinical trial where only the pharmacist and the sponsor know the identity of the IP. The pharmacist has no direct contact with the trial subject and the clinical team. Which of the following BEST describes this trial type? A. Open-label B. Single-blind C. Double-blind D. Triple-blind

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Answer #4

C. Double-blind A-WRONG Open Label: both the researchers and subjects know which treatment is being

administered. B-WRONG: Single blind: subjects are not aware of which treatment is administered.

C-CORRECT: Double-blind the subjects and the researchers are unaware (or blinded) to the treatment being administered.

D-WRONG Triple blind: not a term used in clinical studies

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Question#5 A hypertension trial protocol indicates that subjects should not be randomized on Fridays or Saturdays. During subject screening, a subject meeting all entry criteria is identified. However, the only day that this subject is available for clinic visits is Friday due to his work schedule. The CRC should A. Randomize the subject and make a note to the trial file.

B. Contact the sponsor regarding the subject’s time conflict C. Ask the IRB/IEC for permission to randomize the subject D. Request an exception from the PI

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Answer #5

B. Contact the sponsor regarding the subject’s time conflict

A-WRONG-the CRC is not following the protocol; B-CORRECT- only the sponsor can make changes to the protocol under these circumstances

C-WRONG-the IRB/IEC cannot make changes to the protocol D-WRONG-the PI should not implement any deviations from the protocol

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Question #6 In an effort to increase enrollment in an ongoing trial, the sponsor has broadened inclusion/exclusion criteria to increase the allowable creatinine level. The next step the CRC should take is to A.Notify the IRB/IEC of the change

B. Revise the ICF C. Contact previously ineligible patients D. Document the change in existing subjects’ CRF

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Answer #6

A. Notify the IRB/IEC of the change A-CORRECT: Prior to implementing any changes to the protocol the investigator should notify the IRB/IEC.

B-WRONG There is no indication that this should be done and would not be the first action. No subject could be contact until the protocol change was approved.

D-WRONG there is no reason to do this; the change to the protocol does not affect the inclusion of the current subjects.

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Question #7 At the month-3 visit of a Phase III Double-blind trial, the subject informs the CRC that he was seen in the emergency department for an anaphylactic reaction. The subject states, “The doctor told me I was very lucky. I might have died.” Having received this information, the MOST appropriate sequence of action is to inform the A. PI, Sponsor and IRB/IEC

B. Sponsor, PI, and IRB/IEC C. Sponsor, IRB/IEC and PI D. PI, IRB/IEC and sponsor

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Answer #7

A. PI, Sponsor, and IRB/IEC A-CORRECT- Study PI should be notified first as he/she is responsible for the subjects wellbeing while on the

clinical trial and should ensure that adequate medical care is provided to the subject for all adverse events. Per ICH guidelines, all SAEs should be reported immediately to the study sponsor and to the IRB/IEC per applicable

regulatory requirements. B-WRONG it would not be appropriate to notify the sponsor before making the PI aware of the subject reported

safety information. C-WRONG-it would not be appropriate to notify the sponsor before making the PI aware of subject reported

safety information. D-WRONG-per ICH guidelines, all SAEs should be reported immediately to the study sponsor and to the IRB/IEC

per applicable regulatory requirement.

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Question #8 The subject is participating in a lipid-lowering clinical trial. Before the 12-month visit, the CRC receives an amendment from the sponsor, which includes the addition of the quality-of-life measures to be collected at the 12-month visit. To ensure appropriate collection to this additional data, the CRC should A. Collect the data at the scheduled visit by verbally asking the questions as

indicated in the revised, approved amendment.

B. Assist the subject by providing additional information for questions which the subject states are unclear. C. Schedule the subject for an interim visit as soon as possible, and complete the questionnaire D. Obtain the appropriate signature on the revised, approved consent, then have the subject complete the questionnaires.

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Answer #8

D. Obtain the appropriate signature on the revised, approved consent, then have the subject complete the questionnaires.

A, B, C-WRONG the data should not collected until the IRB approved the revision . D-CORRECT- the reference E6 4.5.2 states that the investigator should not implement any change without favorable approval from the IRB/IEC for a protocol amendment unless there’s a hazard to the subject. The questionnaire does not represent hazard, so nothing should be done without the approval of the IRB/IEC which would include an updated, approved ICF for the amended protocol.

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Question #9 The protocol and protocol summary have been submitted to a central IRB/IEC for review/approval by the CRO prior to the investigators’ meeting. Following the meeting, the entry criteria are altered to facilitate the recruitment and retention of eligible subjects. Prior to trial start-up, the regulatory binder must include 1. An IRB/IEC letter of approval for the amended protocol 2. An IRB/IEC site evaluation form 3. The amended protocol 4. The investigator’s brochure A. 1,2, and 3 only B.1,2,4 and only C. 1,3, and 4 only D. 2,3, and 4 only

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Answer #9

C. 1,3, and 4 only

Of the 4 choices, choice 2-“an IRB/IEC site evaluation form” is the only document not specific to the amendment or IP and not a required regulatory document. Option C is

the only answer that does not include document #2.

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Question #10 A CRA calls to schedule a close-out visit. Per sponsor SOPs, the PI must be present. The CRC informs the CRA that the PI will be out of the country during the period when the CRA would like to visit. The CRC should do which of the following? A. Obtain required PI signatures prior to departure

B. Reschedule the close-out for a later date C. Conduct the visit as long as the PI is available by phone. D. Conduct the visit as long as the sub-investigator is available

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Answer #10

B. Reschedule the close-out for a later date

Per ICH guideline E66.1.38, clinical trial monitoring visits, including close-out visits, should be conducted in accordance with the existing SOPs. A-WRONG- sponsor’s SOPs require the PI to be present at the close-out visit. B-CORRECT- this will allow the PI to be

present for the close-out visit. C-WRONG sponsors SOPs require the PI to be present at the close-out visit. D-WRONG- sponsor’s SOPs require the PI to be present at the close-out visit.

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Question #11 A small biotech company is investigating the anti-tumoral potential of scorpion toxin in high grade recurrent brain tumors. After animal trials have been completed, the first trial in humans would MOST likely involve 1. Healthy volunteers 2. Pharmacokinetic analysis 3. Placebo control 4. Dose escalation A. 1 and 3 only B. 1 and 4 only C. 2 and 3 only D. 2 and 4 only

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Answer #11

D. 2 and 4 only 1-WRONG Phase I trials may be done in healthy volunteers AND certain types of patients (they are NOT always limited to healthy

volunteers). 2-CORRECT Phase I trials are primarily involved with PK sampling. 3. WRONG Phase I may or may not use placebo control; however it would not be ethical in recurrent brain tumor study. 4- CORRECT: Dose escalations are primarily done in Phase I

trials Option D- is the only choice with both of the correct statements.

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Question #12 A CRA calls a CRC to schedule the final monitoring visit. The sponsor requires that the PI be present. The only dates available for the CRA conflict with the PI’s schedule. To prepare for the visit, the CRC should 1. Reschedule the visit 2. Have the PI sign all documents prior to the visit 3. Discard unused trial documents 4. Notify the IRB/IEC

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Answer #12

A. Reschedule the visit A-CORRECT- the sponsor requires that the PI be present.

B-WRONG the PI is required to sign many documents BEFORE the trial commences. C-WRONG unused trial documents should not be discarded until instructed to do so by the sponsor to assure that all essential documents are filed together after the completion of

the trial.

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Question #13 At a screening visit, a CRC takes the following sitting BPs: 168/100 mm Hg 166/104 mm Hg 168/102 mm Hg The patients mean sitting diastolic BP is A. 102 mm Hg B. 103 mm Hg C. 166 mm Hg D. 167 mm Hg

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Answer #13

A. 102 mm Hg

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Question #14 A subject is participating in a lipid-lowering clinical trial. Before his 12-month visit, the CRC receives an amendment from the sponsor that includes an outcomes measurement instrument at the 12-month visit. The CRC should FIRST provide the subject with which of the following? A. An amendment for the subject’s signature

B. A revised consent form C. A copy of the outcomes measurement instrument D. An interpretation of the items on the instrument

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Answer #14

B. A revised consent form A-WRONG Subjects do not sign amendments B-CORRECT of these options this is the document that is signed by a subjects. C and D Wrong These items are intended for

either the investigator or the sponsor/data management.

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Question #15

The trough blood level for a once-daily drug should be drawn how long after the last dose? A. Immediately

B. 4 hours C. 12 hours D. 24 hours

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Answer #15

D. 24 hours Definition of trough (lowest serum concentration level of a drug). This would be defined in the IB. A-WRONG- the trough level

should be measured just before the administration of the next dose. D-CORRECT: the trough level should be measures just before the administration of the next dose.

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Question #16

Which of the following is MOST useful for scheduling trial procedures? A. Site screening log

B. Subject enrollment log C. Trial schedule of events D. Trial team vacation/leave calendar

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Answer #16

C. Trial Schedule of events Consider the following rationale for each option: A-WRONG a screening log does not list time points of study specific procedures

and/or tests. B-WRONG a subject enrollment log does not list time points of study specific procedures and/or tests. C-CORRECT-the trial schedule of events is a framework that helps organize and plan study specific procedures and tests. D-WRONG a

vacation/leave calendar only lists when staff will be out of the office.

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Question #17 The DSMB has prematurely terminated a trial evaluating an investigational pain medication that is taken one tablet orally b.i.d. for chronic hip pain. Subjects are allowed to take one extra caplet per day. Subjects receive a sufficient quantity of IP for 14 days plus two additional doses. Which of the following represents a drug accountability issue? A. Subject A returns 24 pills after 10 days on the trial

B. Subject B returns 12 pills after 8 days on the trial C. Subject C returns 29 pills after 5 days on the trial D. Subject D returns 42 pills after 1 day on the trial

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Answer #17 B. Subject B returns 12 pills after 8 days on the trial

Math Calculations: Amount dispensed= 14 days x 3 pills= 42 +2 additional doses=44; Subject can either take 2 or 3 pills per day. A-WRONG 10 days x 2 pills= 20 44-20= 24

B-CORRECT If subject took 2 pills a day then 8 x 2 =16 and 44-16=28; if subject took 3 pills a day then 8 x 3= 24; and 44-24=20 Either way 12 pills is too few to return; C-WRONG 5 x 3= 15 44-15=29

D-WRONG 1 x 2=2 44-2=42

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Question #18 Twenty-six subjects were enrolled in a pneumonia trial. The site received 100 bottles of IP. Each subject received two bottles. Four subjects did not return their trial bottles. How many bottles are available for the CRC to return to the sponsor at the end of the trial?

A. 44

B. 48 C. 92 D. 96

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Answer #18

C. 92 Math Calculations: 100 (in stock) – (4pts x 2 bottles each)=92

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Question #19 A subject has signed the informed consent form for a hypertension trial. All screening procedures and the physical examination have been completed. The CRC is ready to dispense the single-blind placebo to the subject who asks, “Is that the sugar pill that I read about in that form I signed?” Which of the following should the CRC tell the subject? A. “Only the physician knows what medication you are taking at this time.” B. “I don’t know what you are taking at this time since the trial is blinded.” C. “Yes. Remember everybody has to take the placebo for some time during the trial.” D. It might be the placebo, but we will be checking your blood pressure every week.”

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Answer #19

D. “It might be the placebo, but we will be checking

your blood pressure every week.” Consider the following rationale for each option:

A-WRONG- study is SINGLE-BLIND. Only subject is blinded. B-WRONG-study is SINGLE-BLIND. Only subject is blinded. C-WRONG-study is SINGLE-BLIND. Only subject is blinded. D-CORRECT answer is truthful and keeps subject blinded.

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Question #20

All of the following are regulatory documents EXCEPT A. Informed consent B. Protocol signature page C. Laboratory certification D. Confidentiality agreement

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Answer #20

D. Confidentiality agreement Regulatory documents demonstrate the compliance of the Investigator, Sponsor, and IRB/IEC with the standards of the Good

Clinical Practice and with all applicable regulatory requirements. A-WRONG the informed consent is a regulatory document because it is a process by which a subject confirms willingness to

participate in a trial. This document has to be approved by the IRB/IEC. B-WRONG the protocol signature page is signed by the PI and sponsor to document agreement to the protocol and amendments.

C-WRONG a laboratory certification documents competence of the facility to perform required tests and supports reliability of results.

D-CORRECT: a confidentiality agreement is a nondisclosure contract entered in by the sponsor and the investigator and is not governed by regulatory authorities.

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Pre-Exam Assessment Test current knowledge by completing the questionnaires Code of Federal Regulation – Slides on screen CFR questions –Broader

Good Clinical Practice – The RAN Institute's On Line Training

Campus <http://raninstitute.trainingcampus.net> GCP -More specific

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Special Thanks

Contributors Division/Department/Facility

This presentation was primarily created by Susan Ray

Supervisor Research Coordination Clinical Research Service

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