CRA Credentialing Workbook

Question 1

Explain the general roles and responsibilities of SPONSOR in upholding the protection of subject safety and the validity of data:

Answer 1

Designing the protocol, development of study procedures, and assessment of risks

Question 2

Explain the general roles and responsibilities of INVESTIGATOR in upholding the protection of subject safety and the validity of data:

Answer 2

Reporting AEs and SAE, reporting deviations to IRB, ensuring all staff are qualified with updated licenses and GCP training, supervising the clinical trial medically, compliance with protocol, maintaining proper licensing, completing all the requirements for source documents up to ALCOAC standards, making sure all subjects are consented.

Question 3

Explain the general roles and responsibilities of ETHICS COMMITTEE in upholding the protection of subject safety and the validity of data:

Answer 3

Creating and enforcing guidelines that maintain subject safety, reporting any violations and ensuring investigators who violate ethics are barred from future practice

Question 4

What information from the Investigator’s Brochure should be discussed during the PSV?

Answer 4

During the PSV it is important to discuss the pharmaceutical profile and dosage of the IP, storage/handling expectations, effects in subjects, safety and efficacy, previous study findings in both humans/animals, and potential risks of the IP including AEs/SAEs.

Question 5

What is the FDA list of debarred/disqualified/restricted investigators?
What is the significance of this list and when do we use it within our organization?

Answer 5

The FDA list of debarred/disqualified/restricted investigators is a list of on investigators who have at one point or another failed to comply with governing regulatory agency standards or violated GCP guidelines. This list alerts us of these PIs and allows us to avoid selecting a PI with a history of misconduct

Question 6

What are the requirements for waiving the PSV and what documentation is required?

Answer 6

To waive a PSV the investigator must have been active in a similar study in the last year, the primary facility must be unchanged, PI must be in good standing and not de-barred, have no compliance issues during previous visits, no conflicts with other studies, existing access to eSDV, signed CDA. PSV waiver should be signed by both the sponsor and the project lead.

Question 7

What is the purpose of completing the Source Data Access Survey? What information does it capture?

Answer 7

The Source Data Access Survey exists to ensure investigators understand the source documentation practices expected from their site, explains the type that will be used such as paper or EHR, explain how monitors will access the documents and the archiving process at study completion, and review the source data agreement that will be completed at the SIV, and restrictions that exist and remind the site of ALCOAC principles. All of this helps the monitor verify the site will be able to guarantee that study data integrity is secure and high quality.

Question 8

What is a Case Report Form? Explain how it is used to collect the protocol required data.
What does the CRA review at site to support all CRF entries?

Answer 8

Reports on each visit and all data collected these, the CRA must monitor because this is where our data comes from

Question 9

Explain the key tasks that must be accomplished during a site initiation visit (SIV).

Answer 9

Using the official Syneos Health site activation process and annotated agenda following the site’s regulatory green light, facility tour, source data document review, understanding the protocol, completing site delegation of authority log, IP management training, them agreeing to the project specific monitoring strategy, reviewing GCP training, agreeing to their responsibilities outline in CTA, ensuring facilities are quality and have everything they need.

Question 10

What questions might you ask to determine that the investigator will have adequate subjects to meet the enrollment target for a study?

Answer 10

To determine that the investigator will have adequate subjects to meet the enrollment target, I would ask if they have any exclusion criteria that they find problematic, discuss past performance on studies, and ask if any other similar studies are currently ongoing.

Question 11

What internal and external approvals need to be in place prior to beginning recruitment of subjects?
Explain why it is important that the approvals are in place before subjects are recruited.

Answer 11

Before recruitment can begin the site must complete their SIV and Site Activation Forms must be signed, and the site activation confirmation letter must be sent. This ensures the site is ready to recruit patients.

Question 12

Who should the CRA contact regarding the status of essential documents prior to the SIV? What documents should the CRA collect during the SIV?

Answer 12

The SSUL, and reg group, Prepare for SIV by reviewing project specific info, PSV report, annotated SIV report, safety updates to IB, confirm investigator compliance check, Source data access survey, Collect Delegation of authority log, IP log, enrollment, training logs, consent forms, schedule visit/agenda confirmation letter.

Question 13

What is your responsibility related to Investigational Product during the SIV?
Explain the actions you would take if IP was not on site during the SIV.

Answer 13

Inspecting site facilities, make sure everyone is aware of timelines,
When IP is not yet on site we would monitor using a risk based approach and make sure site will know how to handle it

Question 14

Several questions arise during the protocol discussion during the visit. How do you respond?

Answer 14

If questions arise during the protocol visit I will record all communication and be sure to ask the PI/site staff to list their concerns with the study and send them back to the clinical lead.

Question 15

Define: Adverse Event (AE)

Answer 15

Any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical productand which does not necessarily have a causal relationship with this treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF)

Question 16

Define: Adverse Drug Reaction (ADR)

Answer 16

Pre-approval products : Any noxious and unintended responses to a medicinal product related to any dose (a causal relationship exists between the product and the event) : Marketed products : Any noxious and unintended responses to a medicinal product related to the indicated dose/ dose normally used in man (a causal relationship exists between the product and the event)

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF)

Question 17

Define: Unexpected Adverse Drug Reaction (UADR)

Answer 17

Any ADR in which the nature or severity of which is not consistent with the applicable product information.

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF)

Question 18

Define: Serious Adverse Event (SAE)

Answer 18

Any AE that results in death, was immediately life threatening, resulted in a persistent and significant disability, resulted in a congenital abnormality, resulted in hospitalization or prolongation of an existing hospitalization or other important medical event.

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF), and immediate reporting to sponsor using SAE form

Question 19

Define: Serious Adverse Drug Reaction (SADR)

Answer 19

Any AE that is both related to the IP AND results in either death, was immediately life threatening, resulted in a persistent and significant disability, resulted in a congenital abnormality, resulted in hospitalization or prolongation of an existing hospitalization or other important medical event.

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF), and immediate reporting to sponsor using SAE form

Question 20

Define: Suspected Unexpected Serious Adverse Drug Reaction (SUSAR)

Answer 20

An ADR that is both Serious and Unexpected (unlisted in the IB).
(Disseminated to all concerned investigators, IRB’s, RAs. Death/ life threatening (reported by sponsor to RA in 7 days. All others within 15 days)

Site Reporting Requirements: Source Documents (SD) and Case Report Form (CRF), and immediate reporting to sponsor using SAE form, Site’s IRB

Question 21

During a monitoring visit, the study coordinator hands you a packet of information, which contains 2 IND Safety Reports / SUSARs. She states that she received these several weeks ago from the sponsor and asks you what to do with them. How do you respond?

Answer 21

I would review them with her and respond to the information on the safety reports, notify my clinical lead, and follow up on actions with the safety lead

Question 22

What information about dropouts should be gathered during the trial and why is this an important factor in clinical research?

Answer 22

All safety data and CRF from a follow up visit with them needs to be collected to make sure no subject is having AEs without us knowing

Question 23

Scenario: “Patient initiated study drug in January. In April, she complained of numbness and tingling in her fingers and toes. While still participating in the study, she later reported that she was unable to perform her responsibilities as a seamstress.” Would this be considered a Serious Adverse Event per regulatory definition? Why or why not?

Answer 23

No, this is only an AE since nothing that happened was life threatening or resulted in hospitalization.

Question 24

What storage conditions are typically considered appropriate for an IP?
In what study documents or resources can you find the IP storage requirements?

Answer 24

Typically IP must be stored at room temperature or in a refrigerator. The location must be secure with limited access by anyone but authorized personnel.

Question 25

What key measures are taken to protect subjects in the manufacturing, packaging, labeling and distribution of the IP?

Answer 25

In the US IP manufacturing is subject to strict “Good manufacturing Practice” guidelines, Ip is tested for half-life and purity, IP is temperature controlled and stored away from light/heat during transportation, expiry dates are monitoring, import/export permits must be up to date, and packaging and randomization are overseen by Sponsor/CRO, and import/export permits must be in place.

Question 26

What items do you check to verify that the IP has been used appropriately for the study?
What information can you obtain from each of these items?

Answer 26

It is critical to verify IP handling training was conducted for all site staff involved in IP handling. We can collect training records for all staff on the DAL. We can then obtain the IP log to track dispensation to subjects. We can also verify receipt of IP and supplies on site (study specific medical equipment), collect IP temperature logs, review subject drug accountability and cross checking with source document, and visually inspect the storage facilities and IP inventory and make note of any risks/concerns related to security or other issues. It is critical that a site staff member monitors us while we are with IP to avoid risk of unaccounted for IP.

Question 27

The study that you are closing out has used an electronic/remote data capture system. What are the monitoring actions that will occur during this visit?

Answer 27

a) if DB lock has occurred

b) if DB lock has not occurred